Laser activation can lead to the formation of a layer of aluminum on the surface of aluminum nitride ceramics, thereby preparing metal circuits. Under various gas environments, there are differences in the aluminum layers precipitated by laser-activated aluminum nitride ceramics. The existing literature uses the width of the metal layer to characterize this difference, and these data are very imprecise. Usually, laser energy density is used to describe this processing difference. However, the existing concept of laser energy density is an average value and is not suitable for the threshold of laser activation, because the intensity gradient of the focused Gaussian beam is large, and different intensity distributions represent different energy levels. This article applied a precise concept of laser energy density that sees it as being proportional to light intensity and can be used to evaluate the difference in laser energy density required for the decomposition of aluminum nitride ceramics under various gas bath conditions precisely. Due to the strong energy of a focused Gaussian beam, it is not possible to directly obtain the intensity distribution. Here, the intensity distribution of the collimated beam was used to indirectly obtain the intensity distribution of the focused Gaussian beam, and the threshold values for laser activation under different gas baths were calculated. It was found that the minimum energy density in air increased by 12.5%, and the minimum energy density in nitrogen increased by 3%, using the minimum energy density required for laser activation in argon as the reference. Full article

To investigate the interconnected effects of manufacturing processes on microstructure evolution during hot-rolling, a through process model is required. A novel numerical implementation of the mean-field approach was introduced to efficiently describe the grain growth of larger systems and extended durations. In this approach, each grain is embedded within an average medium and interacts with the average medium, thus avoiding the complexities of individual grain interactions. The proposed upsampling approach dynamically adjusts the simulation grain ensemble, ensuring efficiency and accuracy regardless of the initial number of grains present. This adaptation prevents undersampling artifacts during grain growth. The accuracy of the model is verified against analytical solutions and experimental data, demonstrating high agreement. Moreover, the effects of different initial conditions are successfully investigated, demonstrating the model’s versatility. Due to its simplicity and efficiency, the model can be seamlessly integrated into other microstructure evolution models. Full article

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198–569) and 628 days (95% CI 579–676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282–391 days), and 402 days (95% CI 286–517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs. Full article

Wind field characteristics in a complex topography are significantly influenced by the nature of the surrounding terrains. This study employs onsite measurements to investigate the wind field characteristics at a towering peak protruding out of a steep mountainside, where butterfly−lookalike landscape platform will be constructed; the impact of the surrounding topography on the wind flow is highlighted. The results showed that the blocking effect of the mountains in the mountainous side of the valley caused a significant drop in the mean wind speed from that direction. The stationary test (reverse arrangement test) indicated that the wind speed had a strong nonstationary characteristic, necessitating the employment of a steady and nonstationary wind speed model to assess the wind turbulence characteristics. The three directions’ wind turbulence integral scales were critically influenced by the occurrence of the wind speedup effect, unexpectedly resulting in the vertical turbulence integral scale being the greatest of the three. Furthermore, the measured wind turbulence properties under both wind speed models showed certain variations from the recommended specifications. Consequently, the impact of the local terrain and the speedup effect on the wind characteristics must be thoroughly evaluated to ensure the structural stability of structures installed at a similar topography. Full article

Innovation is the primary driving force for development, and enterprises, as the main drivers of innovation, are an important part of implementing the national innovation strategy. This paper, combining the perspective of the enterprise lifecycle, thoroughly examines the differential impact of the CEO’s financial background on green innovation in enterprises at different stages of the lifecycle. This study finds that the CEO’s financial background has a significant inhibitory effect on green innovation in enterprises, and this conclusion holds true after multiple robustness tests. From the perspective of the lifecycle, it is found that when enterprises are in the mature stage, the CEO’s financial background has a strong inhibitory effect on innovation output. The impact of the CEO’s financial background on green innovation output in the growth stage is relatively weak, while there is no significant impact on green innovation in the declining period. Furthermore, based on the enterprise lifecycle, it is found that the CEO’s financial background has a stronger inhibitory effect on green innovation in non-state-owned enterprises and high-tech industries. The research findings of this paper have important theoretical value and practical significance for promoting green innovation in enterprises and implementing the national innovation strategy. Full article

Abiotic stimuli severely restrict the growth and development of plants, resulting in massive losses in the quality and yield of crops. Exploring genes that can improve crop tolerance to abiotic stress is important. In a previous study, we found that overexpression of the Arabidopsis nucleotide-binding domain leucine-rich repeat (NB-LRR) gene AtRPM1(D505V) increased disease resistance in rice. In this research, we found that AtRPM1(D505V) transgenic plants were more sensitive to abscisic acid (ABA) than wild type (WT) plants. Abiotic-stress resistance in AtRPM1(D505V) transgenic plants was investigated. We found that AtRPM1(D505V) transgenic plants exhibited improved resistance to drought and salt stress; the phonotype and survival rates of transgenic rice were better than WT plants. The expression of stress responsive genes including OsDREB2A, OsDREB2B, OsRD22, and OsRD29A were significantly upregulated in AtRPM1(D505V) overexpressed plants than in WT plants. Moreover, the activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) were significantly increased in AtRPM1(D505V) overexpressed plants than in WT plants under drought and salt stress. Under cold stress, the expression of stress responsive genes and the activities of antioxidant enzymes in AtRPM1(D505V) transgenic plants were significantly lower than in WT plants. Our research demonstrated that AtRPM1(D505V) confers drought and salt resistance to transgenic rice. Therefore, AtRPM1(D505V) could act as a potential candidate gene to cultivate drought- and salt-tolerant plants. Full article

It has been shown that there are thresholds of influence on the response of ecosystem services to their drivers, and the range of drivers that provide high levels of ecosystem services can be delineated through thresholds. However, due to the spatial heterogeneity of landscapes in karst regions, the results of ecosystem service threshold studies in non-karst regions may not be applicable to karst regions. This study explores the threshold effects between ecosystem services in karst landscapes and their natural and social drivers. It is shown that there are nonlinear constraints between them, and different critical thresholds exist for different kinds of ecosystem services. The main thresholds for water supply services include the slope (43.64°) and relief amplitude (331.60 m); for water purification services, they include relief amplitude (147.05 m) and distance to urban land (DTUL) (32.30 km); for soil conservation services, they include the normalized difference vegetation index (NDVI) (0.80) and nighttime light intensity (43.58 nW∙cm⁻²∙sr⁻¹); the main thresholds for biodiversity maintenance services include population density (1481.06 person∙km⁻²) and distance to urban land (DTUL) (32.80 km). This enables regional ecological conservation planning based on different threshold ranges corresponding to different ecosystem services to meet the different needs of different decision makers. Full article

FLT3L-Fc is a half-life extended, effectorless Fc-fusion of the native human FLT3-ligand. In cynomolgus monkeys, treatment with FLT3L-Fc leads to a complex pharmacokinetic/pharmacodynamic (PK/PD) relationship, with observed nonlinear PK and expansion of different immune cell types across different dose levels. A minimal physiologically based PK/PD model with expansion-enhanced target-mediated drug disposition (TMDD) was developed to integrate the molecule’s mechanism of action, as well as the complex preclinical and clinical PK/PD data, to support the preclinical-to-clinical translation of FLT3L-Fc. In addition to the preclinical PK data of FLT3L-Fc in cynomolgus monkeys, clinical PK and PD data from other FLT3-agonist molecules (GS-3583 and CDX-301) were used to inform the model and project the expansion profiles of conventional DC1s (cDC1s) and total DCs in peripheral blood. This work constitutes an essential part of our model-informed drug development (MIDD) strategy for clinical development of FLT3L-Fc by projecting PK/PD in healthy volunteers, determining the first-in-human (FIH) dose, and informing the efficacious dose in clinical settings. Model-generated results were incorporated in regulatory filings to support the rationale for the FIH dose selection. Full article

Background/Objectives: There have been widespread reports of persistent symptoms in both children and adults after SARS-CoV-2 infection, giving rise to debates on whether it should be regarded as a separate clinical entity from other postviral syndromes. This study aimed to characterize the clinical presentation of post-acute symptoms and conditions in the Korean pediatric and adult populations. Methods: A retrospective analysis was performed using a national, population-based database, which was encoded using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). We compared individuals diagnosed with SARS-CoV-2 to those diagnosed with influenza, focusing on the risk of developing prespecified symptoms and conditions commonly associated with the post-acute sequelae of COVID-19. Results: Propensity score matching yielded 1,656 adult and 343 pediatric SARS-CoV-2 and influenza pairs. Ninety days after diagnosis, no symptoms were found to have elevated risk in either adults or children when compared with influenza controls. Conversely, at 1 day after diagnosis, adults with SARS-CoV-2 exhibited a significantly higher risk of developing abnormal liver function tests, cardiorespiratory symptoms, constipation, cough, thrombophlebitis/thromboembolism, and pneumonia. In contrast, children diagnosed with SARS-CoV-2 did not show an increased risk for any symptoms during either acute or post-acute phases. Conclusions: In the acute phase after infection, SARS-CoV-2 is associated with an elevated risk of certain symptoms in adults. The risk of developing post-acute COVID-19 sequelae is not significantly different from that of having postviral symptoms in children in both the acute and post-acute phases, and in adults in the post-acute phase. These observations warrant further validation through studies, including the severity of initial illness, vaccination status, and variant types. Full article

Fermentation parameters, especially the duration, are important in imparting a peculiar taste and flavor to soy sauce. The main purpose of this research was to monitor metabolic changes occurring during the various time intervals of the fermentation process. NMR-based metabolomics was used to monitor the compositional changes in soy sauce during fermentation. The ¹H-NMR spectra of the soy sauce samples taken from the fermentation tanks at 0 to 8 months were analyzed using ¹H-NMR spectroscopy, and the obtained spectra were analyzed by multivariate statistical analysis. The Principal Component Analysis (PCA) and Partial Least Square Discriminate analysis (PLSDA) revealed the separation of samples fermented for various time durations under identical conditions. Key metabolites shown by corresponding loading plots exhibited variations in amino acids (lysine, threonine, isoleucine, etc.), acetate, glucose, fructose, sucrose, ethanol, glycerol, and others. The levels of ethanol in soy sauce increased with longer fermentation durations, which can be influenced by both natural fermentation and the intentional addition of ethanol as a preservative. The study shows that the variation in metabolite can be very efficiently monitored using ¹H-NMR-based metabolomics, thus suggestion to optimize the time duration to get the soy sauce product with the desired taste and flavor. Full article

In this work, passive cooling systems for the revamping of existent silicon photovoltaic (PV) cells were developed and analysed in order to mitigate the efficiency loss caused by temperature rise in the hot season. For this purpose, expanded graphite (EG) was used to stabilize a phase change material (PCM) with a melting temperature close to 53 °C in order to realize thermal management systems (TMSs) able to store heat at constant temperature during melting and releasing it in crystallization. In particular, stearic and palmitic acid mixture (PA-SA) was shape-stabilized in EG at different concentrations (10, 12 and 14 part per hundred ratio) under vacuum into a rotary evaporation apparatus followed by cold compaction; PA-SA leakage was reduced due to its intercalation between the graphite lamellae, and the thermal conductivity necessary to maximize the heat transfer to a bulk TMS was improved via powder cold compaction, which minimizes voids and creates preferential thermal conductive patterns. The composite materials, stable till 150 °C, were tested by differential scanning calorimetry (DSC) at 1 °C/min to precisely determine the phase transition temperatures and the enthalpic content, which was only slightly reduced from 196 J/g of the neat PCM to 169 J/g due to the very low EG fraction necessary for the stabilization. Despite only the 14:100 EG-to-PA-SA ratio, the system’s thermal conductivity was enhanced 40 times with respect to the neat PCM (from 0.2 to 8.3 W/(m K), value never reached in works present in the literature), with a good convergence of the values evaluated through hot disk tests and laser flash analysis (LFA), finding correlation with both graphitic content and density. In order to completely avoid leaking with the consequent dispersion of PCM in the environment during the final application, all the samples were encapsulated in a PE-made film. The mechanical properties were evaluated with compression tests at 30 °C and 80 °C simulating a possible compressive stress deriving from the contact needed to maintain the TMS position on the rear of the PV cells. Finally, the material response was simulated by imposing thermal cycles into a climatic chamber and reproducing the three hottest and coldest days of summer 2022 of two Italian locations, Verona (Veneto, 45° N, 11° E) and Gela (Sicily, 37° N, 14° E), thus highlighting the thermal management effects with delays in temperature increase and daily peak temperature smoothing. The role of EG is strategic for the processing and the properties of the resulting composites in order to realize a proper compromise between the melting enthalpy of PCM and the thermal conductivity enhancement given by EG. Full article

This study explores trust dynamics within online social networks, blending social science theories with advanced machine-learning (ML) techniques. We examine trust’s multifaceted nature—definitions, types, and mechanisms for its establishment and maintenance—and analyze social network structures through graph theory. Employing a diverse array of ML models (e.g., KNN, SVM, Naive Bayes, Gradient Boosting, and Neural Networks), we predict connection strengths on Facebook, focusing on model performance metrics such as accuracy, precision, recall, and F1-score. Our methodology, executed in Python using the Anaconda distribution, unveils insights into trust formation and sustainability on social media, highlighting the potent application of ML in understanding these dynamics. Challenges, including the complexity of modeling social behaviors and ethical data use concerns, are discussed, emphasizing the need for continued innovation. Our findings contribute to the discourse on trust in social networks and suggest future research directions, including the application of our methodologies to other platforms and the study of online trust over time. This work not only advances the academic understanding of digital social interactions but also offers practical implications for developers, policymakers, and online communities. Full article

In order to reduce the toxicological impact on healthy cells and to improve the therapeutic response, many drug delivery systems have been fabricated and analysed, involving the use of different natural and synthetic materials at macro-, micro- and nanoscales. Among the natural materials which have demonstrated a huge potential for the development of effective drug delivery systems, silk fibroin has emerged for its excellent biological properties and for the possibility to be processed in a wide range of forms, which can be compliant with multiple active molecules and pharmaceutical ingredients for the treatment of various diseases. This review aims at presenting silk fibroin as an interesting biopolymer for applications in drug delivery systems, exploring the results obtained in recent works in terms of technological progress and effectiveness in vitro and in vivo. Full article

Background and Objectives: This study aimed to evaluate the mid-term effectiveness and safety of a combined ultrasound (US) and fluoroscopy (FL)-guided approach in comparison to US-guided and FL-guided caudal epidural steroid injections (CESI) for treating unilateral lower lumbar radicular pain. Materials and Methods: A total of 154 patients who underwent CESI between 2018 and 2022 were included. Patients were categorized into three groups based on the guidance method: combined US and FL (n = 51), US-guided (n = 51), and FL-guided (n = 52). The study design was retrospective case-controlled, utilizing patient charts and standardized forms to assess clinical outcomes, adverse events, complications during the procedures. Results: In all groups, Oswestry Disability Index and Verbal Numeric Scale scores improved at 1, 3, and 6 months after the last injection, with no significant differences between groups (p < 0.05). The treatment success rate at all time points was also similar among the groups. Logistic regression analysis showed that injection method, cause, sex, age, number of injections, and pain duration did not independently predict treatment success. Blood was aspirated before injection in 2% (n = 1), 13.5% (n = 7), and 4% (n = 2) of patients in the combined US and FL groups, FL-guided groups, and US-guided groups, respectively. Intravascular contrast spread was detected in one patient in the combined method groups and seven in the FL-guided groups. Conclusions: When comparing pain reduction and functional improvement, there was no significant difference between the three methods. The combined method took less time compared to using FL alone. The combined approach also showed a lower occurrence of intravascular injection compared to using FL alone. Moreover, blood vessels at the injection site can be identified with an ultrasound using the combined method. Given these advantages, it might be advisable to prioritize the combined US- and FL-guided therapy when administering CESI for patients with unilateral lumbar radicular pain. Full article

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city. Full article

Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery. Full article

The universal newborn hearing screening (NHS) program was implemented in Russia in 2008 to replace the high-risk newborn hearing screening. More than 95% coverage and significant improvement in early detection and intervention is achieved. Meanwhile, it was shown that current OAE-based hearing screening missed 13% of newborns with genetically ascertained hereditary sensorineural hearing loss (SNHL). The aim of the study is to assess the results of genetic investigation and NHS in a large cohort of Russian children with bilateral SNHL and to study the feasibility of implementation of combined hearing and genetic screening in Russia. Genetic, audiological and NHS data of 1292 pediatric patients with bilateral SNHL born in 2008–2021 were analyzed. GJB2 sequencing was performed for all subjects, 644 patients had pathological GJB2 genotype, 406 of them were homozygous for c.35delG variant. The group of 155 GJB2-negative patients were searched for other SNHL genes, The pathological genotypes were identified at 87 patients. The most frequent genes were STRC (21.8%), USH2A (16.1%), OTOF (8%) and SLC26A4 (6.9%). Children with confirmed genetic etiology passed NHS in 21% of cases. The perspectives of implementation of national comprehensive newborn hearing and genetic screening including whole exome sequencing technologies are discussed. Full article

Talaromyces sp. DC2 is an endophytic fungus that was isolated from the stem of Catharanthus roseus (L.) G. Don in Hanoi, Vietnam and is capable of producing vinca alkaloids. This study utilizes the PacBio Sequel technology to completely sequence the whole genome of Talaromyces sp. DC2The genome study revealed that DC2 contains a total of 34.58 Mb spanned by 156 contigs, with a GC content of 46.5%. The identification and prediction of functional protein-coding genes, tRNA, and rRNA were comprehensively predicted and highly annotated using various BLAST databases, including non-redundant (Nr) protein sequence, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Carbohydrate-Active Enzymes (CAZy) databases. The genome of DC2 has a total of 149, 227, 65, 153, 53, and 6 genes responsible for cellulose, hemicellulose, lignin, pectin, chitin, starch, and inulin degradation, respectively. The Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) analyses revealed that strain DC2 possesses 20 biosynthetic gene clusters responsible for producing secondary metabolites. The strain DC2 has also been found to harbor the DDC gene encoding aromatic L-amino acid decarboxylase enzyme. Conclusively, this study has provided a comprehensive understanding of the processes involved in secondary metabolites and the ability of the Talaromyces sp. DC2 strain to degrade plant cell walls. Full article

The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE’s low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of Pneumocystis pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE’s national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE. Full article

The development of fully biobased hydrogels obtained by simple routes and in the absence of toxic or environmentally harmful reagents is a major challenge in meeting new societal demands. In this work, we discuss the development of hydrogels made from cellulose nanocrystals (CNCs) and xyloglucan (XG), two non-toxic, renewable, and biobased components. We present three strategies to fine-tune the functional properties. The first one consists in varying the XG/CNC ratio that leads to the modulation of the mechanical properties of hydrogels as well as a better comprehension of the gel mechanism formation. The second relies on tuning the XG chains’ interaction by enzymatic modification to achieve thermoresponsive systems. Finally, the third one is based on the increase in the hydrogel solid content by osmotic concentration. The high-solid-content gels were found to have very high mechanical properties and self-healing properties that can be used for molding materials. Overall, these approaches are a case study of potential modifications and properties offered by biobased nanocolloidal hydrogels. Full article

Background: The diagnosis of depression in dementia patients leads to an increase in the burden of the disease. To treat depression in this patient group, antidepressants are frequently used; however, there is not any proof of their therapeutic effectiveness, and their use may be potentially harmful. This narrative review aims to summarize the existing evidence regarding the role of antidepressants in treating depression in dementia patients. Main text: A search was conducted in the PubMed, Excerpta Medica database (EMBASE), and Cochrane databases for randomized controlled trials and meta-analyses wherein antidepressants were given to dementia sufferers to address depression. Fifteen randomized controlled trials and seven meta-analyses were identified. Most well-designed blinded placebo-controlled trials reported a lack of effectiveness of antidepressants in treating depression in dementia patients. Among the seven metanalyses, two reported good efficacy of Selective serotonin reuptake inhibitors (SSRIs). However, two major Cochrane reviews reported little or no effectiveness and increased side effects of antidepressants in dementia patients. Conclusion: There is robust evidence regarding the lack of efficacy of antidepressants in treating depression in dementia patients. However, further well-designed Randomized controlled trials (RCTs,) using scales with good validity and reliability to diagnose depression in dementia patients, sufficient sample sizes, and detailed adverse effect profiles may help determine the rationale for their use. Full article

Intervertebral disc degeneration (IVDD) is a worldwide disease that causes low back pain and reduces quality of life. Biotherapeutic strategies based on tissue engineering alternatives, such as intervertebral disc scaffolds, supplemented by drug-targeted therapy have brought new hope for IVDD. In this study, to explore the role and mechanism of MnO₂/GelMA composite hydrogels in alleviating IVDD, we prepared composite hydrogels with MnO₂ and methacrylate gelatin (GelMA) and characterized them using compression testing and transmission electron microscopy (TEM). Annulus fibrosus cells (AFCs) were cultured in the composite hydrogels to verify biocompatibility by live/dead and cytoskeleton staining. Cell viability assays and a reactive oxygen species (ROS) probe were used to analyze the protective effect of the composite hydrogels under oxidative damage. To explore the mechanism of improving the microenvironment, we detected the expression levels of antioxidant and autophagy-related genes and proteins by qPCR and Western blotting. We found that the MnO₂/GelMA composite hydrogels exhibited excellent biocompatibility and a porous structure, which promoted cell proliferation. The addition of MnO₂ nanoparticles to GelMA cleared ROS in AFCs and induced the expression of antioxidant and cellular autophagy through the common SIRT1/NRF2 pathway. Therefore, the MnO₂/GelMA composite hydrogels, which can improve the disc microenvironment through scavenging intracellular ROS and resisting oxidative damage, have great application prospects in the treatment of IVDD. Full article