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Abstract Toe fringes are a key innovation for sand dwelling lizards, and the relationship between toe fringe function and substrate properties is helpful in understanding the adaptation of lizards to sand dune environments. We tested the sand burial performance of Phrynocephalus mystaceus on different sand substrates with toe fringe manipulation, with the aim of assessing whether the function of the toe fringes shifts under different substrate properties, especially in highly mobile substrates. The sand burial performance of P. mystaceus was influenced by substrate properties in relation to the toe fringe states of the lizard. After removal of the bilateral toe fringes, the sand burial ability score of P. mystaceus was significantly higher on sand substrates below 100 mesh than on native sand substrates. As the angle of stability of the substrate properties decreased, the sand burial performance of the lizard was even better after the bilateral toe fringes were removed. The results of the LASSO model and the path analysis model showed that the stability angle provided the opposite effect on sand burial performance in different toe fringe states. These results further suggest that the sand burial function of toe fringes may not be suitable for highly mobile sand substrates. It remains to be tested further whether the function of toe fringes is more important for running on sand.

Abstract Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4’s potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab’s efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge.

Abstract Developing high-performance Pt-based catalysts with low Pt loading is crucial but challenging for CO oxidation at temperatures below 100 °C. Herein, we report a Pt-based catalyst with only a 0.15 wt% Pt loading, which consists of Pt–Ti intermetallic single-atom alloy (ISAA) and Pt nanoparticles (NP) co-supported on a defective TiO2 support, achieving a record high turnover frequency of 11.59 s–1 at 80 °C and complete conversion of CO at 120 °C. This is because the coexistence of Pt–Ti ISAA and Pt NP significantly alleviates the competitive adsorption of CO and O2, enhancing the activation of O2. Furthermore, Pt single atom sites are stabilized by Pt–Ti ISAA, resulting in distortion of the TiO2 lattice within Pt–Ti ISAA. This distortion activates the neighboring surface lattice oxygen, allowing for the simultaneous occurrence of the Mars-van Krevelen and Langmuir–Hinshelwood reaction paths at low temperatures.

Abstract Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.

The protective effect and underlying mechanism of melatonin (MT) treatment against Rhizopus stolonifer in postharvest peach fruit (Prunus persica (L.) Batsch cv ‘Xiahui 8’) were studied. Freshly harvested peaches were inoculated with R. stolonifer following pretreatment with different concentrations of MT (0, 0.05, 0.10, 0.50 and 1.00 mmol/L) and then stored at 20 ℃ for up to 60 h. Disease development was measured to determine the most effective MT concentration. Subsequently, the effects of MT treatment on quality parameters, total phenol and lignin contents, disease resistance-related enzyme activity and gene expression in peaches during postharvest storage, and the in vitro growth of R. stolonifer were investigated. The results showed that 0.50 mmol/L MT treatment could most significantly reduce the occurrence of Rhizopus rot and maintain postharvest fruit quality. Furthermore, compared with either of them alone, R. stolonifer inoculation after MT treatment exhibited stronger disease resistance response, resulting in a marked increase in the activities of chitinase (CHI), β-1,3-glucanase (GLU), phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), peroxidase (POD) and polyphenol oxidase (PPO), the contents of total phenols and lignin, and the expression levels of defense-related genes such as those encoding CHI (PpCHI), GLU (PpGLU), PAL (PpPAL) and POD (PpPOD). Moreover, MT treatment had no significant inhibitory effect on the growth of R. stolonifer in vitro. Taken together, these results indicate that MT can initiate defense responses to pathogenic infection indirectly by priming defense, thereby reducing the occurrence of peach postharvest diseases.

Abstract Background Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem. Methods This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score. Discussion Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function. Trial registration Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .

Abstract Machine learning algorithms are frequently used to clinical risk prediction. Our study was designed to predict risk factors of prolonged intra-aortic balloon pump (IABP) use in patients with coronary artery bypass grafting (CABG) through developing machine learning-based models. Patients who received perioperative IABP therapy were divided into two groups based on their length of IABP implantation longer than the 75th percentile for the whole cohort: normal (≤ 10 days) and prolonged (> 10 days) groups. Seven machine learning-based models were created and evaluated, and then the Shapley Additive exPlanations (SHAP) method was employed to further illustrate the influence of the features on model. In our study, a total of 143 patients were included, comprising 56 cases (38.16%) in the prolonged group. The logistic regression model was considered the final prediction model according to its most excellent performance. Furthermore, feature important analysis identified left ventricular end-systolic or diastolic diameter, preoperative IABP use, diabetes, and cardiac troponin T as the top five risk variables for prolonged IABP implantation in patients. The SHAP analysis further explained the features attributed to the model. Machine learning models were successfully developed and used to predict risk variables of prolonged IABP implantation in patients with CABG. This may help early identification for prolonged IABP use and initiate clinical interventions.

The superhydrophobic coating can effectively prevent the intrusion, adhesion and condensation of water-containing corrosive media on the surface. However, the poor mechanical and chemical stability of traditional superhydrophobic coatings significantly limits their application in complex and harsh environments. In this study, a superhydrophobic PDMS-EP@SiO2-GO coating was formed on the surface of Q345 steel sheets by using a composite substrate of graphene oxide(GO) and nano silicon dioxide(SiO2) with polydimethylsiloxane(PDMS) and epoxy resin(EP), combined with spraying technology. The superhydrophobic, self-cleaning, anti-fouling, mechanical wear resistance, chemical corrosion resistance and anti-corrosion properties of the coating were studied. Results showed that the water contact angle of PDMS-EP@SiO2-GO was 166.57°, and the sliding angle was less than 3°. Due to the strengthening effect of GO on the coating substrate, the coating maintained a contact angle of more than 155° for liquids with water temperatures ranging from 20 ℃ to 100 ℃ and a contact angle of more than 160° for acidic/alkaline solutions. The sliding angle was less than 4° under the above conditions. After sandpaper friction(total friction length of 40 m) and 30 cycles of tape-peeling tests, the coating still exhibited good superhydrophobic ability, with the contact angle remaining above 152°. In addition, PDMS-EP@SiO2-GO, with excellent water resistance, demonstrated good anti-fouling and self-cleaning properties. In terms of corrosion protection, the lowest frequency impedance of PDMS-EP@SiO2-GO increased by an order of magnitude, and the charge transfer resistance increased by two orders of magnitude, showing excellent corrosion resistance. PDMS-EP@SiO2-GO addressed the problem of weak mechanical and chemical stability in traditional superhydrophobic coatings and enabled the persistent protection of the metal substrate. The as-prepared superhydrophobic coating, with good practicability, contributes to the safe and reliable service of mechanical equipment throughout its life cycle.

Ischemic stroke (IS) is a major cause of mortality and morbidity worldwide. Beyond thrombolysis, strategies targeting anti-oxidative apoptosis and angiogenesis are considered prospective therapeutic strategies. Nevertheless, existing natural and clinical remedies have limited efficacy in the management of IS. Moreover, despite their millennial legacy of IS remediation, natural remedies such as ginseng incur high production costs. The novel glycopeptide APMCG-1, extracted from mountain-cultivated ginseng dregs in our previous study, is a potent therapeutic candidate for IS. This study investigated APMCG-1's remedial mechanisms against IS injury using an H2O2-induced oxidative stress paradigm in human umbilical vein endothelial cells (HUVECs) emulating ischemic endothelial cells, in a ponatinib-induced zebrafish IS model, and in rat middle cerebral artery occlusion (MCAO) prototypes. Cellular assays confirmed the proficiency of APMCG-1 in preventing oxidative stress and cell death, fostering regeneration, and facilitating neovascularization within the H2O2-stressed HUVECs framework. Moreover, APMCG-1 augmented hemodynamic velocity, oxidative stress mitigation, apoptosis reduction, and motor enhancement in a zebrafish model of IS. In MCAO rats, APMCG-1 ameliorated neurological deficits and cerebral injury, as evidenced by increased neurological scores and diminished infarct dimensions. In cells and animal models, APMCG-1 activated the PI3K/AKT signaling pathway, modulating factors such as Nrf2, Bcl-2, Caspase 3, eNOS, and VEGFA, thereby ameliorating cellular oxidative distress and catalyzing angiogenesis. Collectively, these results demonstrate the potential protective effects of APMCG-1 in IS pharmacotherapy and its prospective utility as an herbal-derived IS treatment modality.

As the prevalence of obesity continues to rise globally, the research on adipocytes has attracted more and more attention. In the presence of nutrient overload, adipocytes are exposed to pressures such as hypoxia, inflammation, mechanical stress, metabolite, and oxidative stress that can lead to organelle dysfunction. Endoplasmic reticulum (ER) is a vital organelle for sensing cellular pressure, and its homeostasis is essential for maintaining adipocyte function. Under conditions of excess nutrition, ER stress (ERS) will be triggered by the gathering of abnormally folded proteins in the ER lumen, resulting in the activation of a signaling response known as the unfolded protein responses (UPRs), which is a response system to relieve ERS and restore ER homeostasis. However, if the UPRs fail to rescue ER homeostasis, ERS will activate pathways to damage cells. Studies have shown a role for disturbed activation of adipocyte ERS in the pathophysiology of obesity and its complications. Prolonged or excessive ERS in adipocytes can aggravate lipolysis, insulin resistance, and apoptosis and affect the bioactive molecule production. In addition, ERS also impacts the expression of some important genes. In view of the fact that ERS influences adipocyte function through various mechanisms, targeting ERS may be a viable strategy to treat obesity. This article summarizes the effects of ERS on adipocytes during obesity.

Neurofibromatosis type 1 (NF-1) is commonly associated with a variety of rare tumors. However, no case of multiple gastric gastrointestinal stromal tumors (GISTs) or duodenal ampulla neuroendocrine tumors (NETs) with multiple liver metastases in a patient with NF-1 has yet been reported. Here, we describe a case of a 55-year-old female patient with NF-1 whose serum Pro-Gastrin-Releasing Peptide (pro-GRP) levels were elevated. Gastrointestinal endoscopy and biopsy showed duodenal papilla space-occupying mass, and the pathological diagnosis turned out to be neuroendocrine tumors (NETs). During surgical exploration, multiple tumors were found on the serosal surface of the stomach and numerous miliary metastases in the liver. Following histopathological examination, it was determined that the liver metastases were NF-1 and the tumors in the gastric wall were GISTs. The patient benefited from targeted therapy and had an uneventful hospital stay. In this case, we emphasize treating patients with neurofibromatosis type 1 who exhibit abdominal symptoms with a high degree of clinical suspicion and performing thorough evaluations to rule out multiple tumors.

BackgroundHypertension (HT) is a common chronic disease in older adults. It not only leads to dizziness and other symptoms affecting balance in older adults with HT but also affects the hemodynamics of the cerebral cortex. At present, potential neural mechanisms of balance control in older adults with HT are still unclear. Therefore, this study aimed to explore the differences in the center of pressure (COP) and cerebral cortex activation between older adults with HT and normotension (NT) during standing balance tasks. This study May provide guidance for the early detection of the risk of falls among older adults with HT and the development of clinical rehabilitation strategies.MethodsIn this cross-sectional study, 30 older adults with NT (NT group) and 27 older adults with HT (HT group) were subjected to three conditions: task 1, standing with eyes open on a stable surface; task 2, standing with eyes closed on a stable surface; and task 3, standing with eyes open on the surface of the foam pad. Cortical hemodynamic reactions were measured using functional near-infrared spectroscopy, and COP parameters were measured using a force plate.ResultsThe mean velocity of the COP in the medial–lateral direction in the NT group was significantly higher than that in the HT group (F = 5.955, p = 0.018) during task 3. When proprioception was disturbed, the activation of the left premotor cortex and supplementary motor cortex in the HT group was significantly lower than that in the NT group (F = 14.381, p

This study aimed to investigate the effect of ultrasound (US) treatment on the quality maintenance of fresh-cut broccoli during storage. Fresh-cut broccoli was treated ultrasonically at 40 kHz and different power levels (200, 250, 300, 350 and 400 W) for 10 min and then stored at 10 ℃ for up to 96 h. The changes of appearance and microbial load were measured to determine the optimum parameters of US treatment for fresh-cut broccoli. Furthermore, the effect of the optimum US treatment on chlorophyll degradation and the changes in bioactive components in fresh-cut broccoli was studied. The obtained data indicated that US treatments at all power levels tested delayed the increase of yellowing index, L* value, total mold and yeast count and total bacterial count, and inhibited the decrease of H value, the 300 W power being the most effective in maintaining the appearance and microbial quality of fresh-cut broccoli. US treatment at 300 W effectively inhibited the activities of chlorophyllase and Mg-dechelatase, contributing to maintaining higher contents of chlorophyll a, chlorophyll b and total chlorophyll of fresh-cut broccoli. Meanwhile, this treatment maintained higher contents of bioactive ingredients such as vitamin C, total phenols, total glucosinolates and sulforaphane, and improved the scavenging capacity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. Therefore, these results indicated that US treatment could not only effectively slow down the yellowing of fresh-cut broccoli, but also maintain higher contents of bioactive compounds, thus playing a fresh-keeping role.

Abstract The flow of fluid through the porous matrix of a reservoir rock applies a seepage force to the solid rock matrix. Although the seepage force exerted by fluid flow through the porous matrix of a reservoir rock has a notable influence on rock deformation and failure, its effect on hydraulic fracture (HF) propagation remains ambiguous. Therefore, in this study, we improved a traditional fluid–solid coupling method by incorporating the role of seepage force during the fracturing fluid seepage, using the discrete element method. First, we validated the simulation results of the improved method by comparing them with an analytical solution of the seepage force and published experimental results. Next, we conducted numerical simulations in both homogeneous and heterogeneous sandstone formations to investigate the influence of seepage force on HF propagation. Our results indicate that fluid viscosity has a greater impact on the magnitude and extent of seepage force compared to injection rate, and that lower viscosity and injection rate correspond to shorter hydraulic fracture lengths. Furthermore, seepage force influences the direction of HF propagation, causing HFs to deflect towards the side of the reservoir with weaker cementation and higher permeability.

Abstract Cohort and case-control data have suggested an association between low to moderate alcohol consumption and decreased risk of ischemic heart disease (IHD), yet results from Mendelian randomization (MR) studies designed to reduce bias have shown either no or a harmful association. Here we conducted an updated systematic review and re-evaluated existing cohort, case-control, and MR data using the burden of proof meta-analytical framework. Cohort and case-control data show low to moderate alcohol consumption is associated with decreased IHD risk – specifically, intake is inversely related to IHD and myocardial infarction morbidity in both sexes and IHD mortality in males – while pooled MR data show no association, confirming that self-reported versus genetically predicted alcohol use data yield conflicting findings about the alcohol-IHD relationship. Our results highlight the need to advance MR methodologies and emulate randomized trials using large observational databases to obtain more definitive answers to this critical public health question.

Abstract Background Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development. Methods We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues. Results lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth. Conclusion This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.

Abstract Major depressive disorder (MDD) is a serious mental illness, characterized by disturbances of gut microbiome, it is required to further explore how the carbohydrate-active enzymes (CAZymes) were changed in MDD. Here, using the metagenomic data from patients with MDD (n = 118) and heath controls (HC, n = 118), we found that the whole CAZymes signatures of MDD were significantly discriminated from that in HC. α-diversity indexes of the two groups were also significantly different. The patients with MDD were characterized by enriched Glycoside Hydrolases (GHs) and Polysaccharide Lyases (PLs) relative to HC. A panel of makers composed of 9 CAZymes mainly belonging to GHs enabled to discriminate the patients with MDD and HC with AUC of 0.824. In addition, this marker panel could classify blinded test samples from the two groups with an AUC of 0.736. Moreover, we found that baseline 4 CAZymes levels also could predict the antidepressant efficacy after adjusted confounding factors and times of depressive episode. Our findings showed that MDD was associated with disturbances of gut CAZymes, which may help to develop diagnostic and predictive tools for depression.

Climate change alters the intensity and frequency of drought and rewetting (D/W) events; however, the influence patterns of D/W on soil N2O efflux in the water-limited area were not fully understood. Therefore, the impacts of D/W cycles varying in different extent of rewetting and frequency to N2O efflux in two kinds of soil on the Loess Plateau were investigated. The incubation conditions consisted of 1) D/W treatments with four 7-day cycles from 10% water holding capacity (WHC) to 60%WHC or 90%WHC, 2) constant moisture of 60%WHC and 90%WHC. The pulse of N2O efflux rate under 10−60%WHC treatment was higher than that under 10−90%WHC treatment in calcic cambisols, while opposite trend was observed in earth-cumuli-orthic anthrosols. Meanwhile, the pulse of N2O efflux rate decreased as cycle number increased for different wetting intensities and soil types. The direct N2O efflux under 10−60%WHC and 10−90%WHC treatments were 5.49 and 1.89 μg N2O–N g−1 soil in calcic cambisols, with those being 1.92 and 10.85 μg N2O–N g−1 soil in earth-cumuli-orthic anthrosols, respectively. The N loss in earth-cumuli-orthic anthrosols was approximately 5.74 times greater than that in calcic cambisols under 10−90%WHC treatment, whereas the N loss under 10−60%WHC treatment was about 2.86 times greater in calcic cambisols than that in earth-cumuli-orthic anthrosols. This study suggested that extreme rainfall events can enhance the N2O efflux and N loss in agricultural soils on the Loess Plateau in terms of soil type and wetting intensity, which should not be ignored in the N fertilizer management.

It is well known that calcium oxide (CaO) has better catalytic efficiency than most heterogeneous catalysts in many transesterification reactions. However, the gradual deactivation problem prevents its large-scale application in industry. In this paper, the deactivation mechanism of CaO in a fixed-bed reactor is investigated based on the transesterification reaction of propylene carbonate and methanol. The leaching amount of CaO during the reaction was estimated by the concentration of Ca in the products. The pretreated and recovered catalysts were characterized by FT-IR, XRD, TG-MS and SEM-EDS. It is evident from experiments and characterization that the deactivation process of CaO is accompanied by the leaching of calcium species and the generation of CaCO3, which are also verified by DFT calculations. At high temperature and high weight hourly space velocity, the deactivation was attributed to the formation of dense CaCO3 shell, which prevents the contact between the feedstock and the active species inside.

Abstract The mechanism involved in major depressive disorder (MDD) is well‐studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single‐cell RNA‐sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA‐seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen‐activated protein kinases (MAPK) pathway is identified. E‐twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

Ectopic calcification of the renal interstitium as an important cause of renal stone formation. Hydroxycitric acid (HCA), a derivative of citric acid, has antioxidant properties and inhibits the crystallisation of calcium salts.The study found that HCA has an inhibitory effect on calcification and calcium salt deposition in fibroblasts. Additionally, HCA was found to reduce calcification-induced oxidative damage and apoptosis.Animal experiments also showed that HCA reduced calcium salt deposition and expression of calcification-related proteins. Cellular transcriptomic analysis demonstrated that HCA can regulate the changes in cellular transcriptome caused by calcification in culture. HCA can effectively inhibit the calcification of renal interstitial fibroblasts, reducing the risk of stone formation by inhibiting calcification culture-induced apoptosis and calcium salt deposition. Therefore, HCA is a promising alternative drug for inhibiting renal stone formation.

Background White adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus. However, the internal regulatory mechanisms underlying are still unknown. Methods and results We generated adipocyte‐specific FAK KO (FAK‐AKO) mice and investigated their phenotype. The cascade of adipocyte, macrophage in adipocyte tissues, and pancreatic β‐cells were proposed in FAK‐AKO mice and validated by cell line studies using 3T3‐L1, Raw264.7 and Min6. The FAK‐AKO mice exhibited glucose intolerance, reduced adipose tissue mass and increased apoptosis, lipolysis and inflammatory response in adipose tissue. We further demonstrate that adipocyte FAK deletion increases β cell apoptosis and inflammatory infiltrates into islets, which is potentiated if mice were treated with STZ. In the STZ‐induced diabetes model, FAK AKO mice exhibit less serum insulin content and pancreatic β cell area. Moreover, serum pro‐inflammatory factors increased and insulin levels decreased after glucose stimulation in FAK AKO mice. In a parallel vitro experiment, knockdown or inhibition of FAK during differentiation also increased apoptosis, lipolysis and inflammatory in 3T3‐L1 adipocytes, whereas the opposite was observed upon overexpression of FAK. Moreover, coculturing LPS‐treated RAW264.7 macrophages with knockdown FAK of 3T3‐L1 adipocytes increased macrophage pro‐inflammatory response. Furthermore, conditioned medium from above stimulated Min6 cells apoptosis (with or without STZ), whereas the opposite was observed upon overexpression of FAK. Mechanistically, FAK protein interact with TRAF6 in adipocytes and knockdown or inhibition of FAK activated TRAF6/TAK1/NF‐κB signaling, which exacerbates inflammation of adipocytes themselves. Conclusion Adipocyte FAK deletion promotes both adipocyte apoptosis and adipose tissue inflammation. Pro‐inflammatory factors released by the FAK‐null adipose tissue further trigger apoptosis in pancreatic islets induced by the administration of STZ, thereby exacerbating the diabetes mellitus. This study reveals a link between FAK‐mediated adipose inflammation and diabetes mellitus, a mechanism that has not been previously recognized.