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Wen Jing Sun,1,2 Yu Jin Liu1 1Department of Nursing Welfare, Changchun Humanities and Sciences College, Changchun, Jilin, 130117, People’s Republic of China; 2Department of Counseling Psychology, Dongshin University, Naju-si, Jeollanam, Republic of KoreaCorrespondence: Wen Jing Sun, Department of Nursing Welfare, Changchun Humanities and Sciences College, No. 1488, Boshuo Road, Jingyue National High-Tech Industrial Development Zone, Changchun City, Jilin, 130117, People’s Republic of China, Tel +8615904405614, Email 179403066@qq.comPurpose: The aim of this study was to investigate the sleep quality as well as the influence of social support on the sleep quality of elderly people in nursing homes in northeast China, and analyze the chain-mediating role of psychological adjustment and coping styles in social support and sleep quality, thereby to provide a scientific basis for the development of effective intervention measures in this direction.Patients and Methods: This study was conducted during January–March 2023 and adopted a cluster sampling method to select 5 elderly care institutions from across the Jilin, Liaoning, and Heilongjiang provinces in Northeast China. A questionnaire survey was conducted using the Self-mate General Situation Questionnaire, Pittsburgh Sleep Quality Index, Nursing Home Adjustment Scale for the Elderly, Social Support Rating Scale, and Medical Coping Modes Questionnaire. Statistical analysis methods, including ANOVA, logistic multi-factor regression, and Pearson’s correlation were employed in SPSS 26.0, while Amos 26.0 was used to build a structural equation model to analyze the interaction path and the mediating role between the variables.Results: The sleep quality of elderly individuals in elderly care institutions was relatively low 8.43(3.456). Social support of elderly individuals in elderly care institutions affected their sleep quality through i) both psychological adjustment and face-to-face coping style (B = 0.493, P < 0.001, 95% CI = 0.050– 0.122) and ii) both psychological adjustment and avoidance coping style (B = − 0.302, P < 0.001, 95% CI = − 0.119 to − 0.048). Psychological adjustment, confrontation coping, and avoidance coping played a mediating role in the sequential relationship between social support and the sleep quality of elderly individuals in elderly care institutions.Conclusion: Psychological adjustment and coping styles have a chain-mediating effect between social support and sleep quality of the elderly in northeast China’s elderly care institutions.Keywords: elderly care institutions, elderly people, sleep quality, psychological adjustment, social support, nursing

Yu-Fei Qian,1 Gui-Ling Geng,1 Yu-Qin Ren,2 Xin-Tong Zhang,2 Wen-Jun Sun,2 Qing Li2 1Department of School of Nursing, Nantong University Medical School, Nantong, 226001, People’s Republic of China; 2Department of Emergency, Nantong First People’s Hospital, Nantong, 226006, People’s Republic of ChinaCorrespondence: Gui-Ling GengDepartment of School of Nursing, Nantong university Medical school, No. 19, Qixiu Road, Nantong City, Jiangsu Province, 226001, People’s Republic of ChinaTel +86 15152889466Fax +86-513-85051876Email geng_gl@126.comObjective: This study aimed to investigate community residents’ awareness of basic life support (BLS) and their willingness to attempt rescue.Methods: From October to December 2020, in the communities of Nantong City, a stratified three-stage random sampling method was adopted to select residents from 12 neighborhood committees over the age of 18 with whom to conduct a cross-sectional questionnaire survey. A self-designed questionnaire was adopted, the contents of which included the general situation of the respondent, knowledge, attitude, and behavior in relation to BLS; the Cronbach’s α coefficient of the questionnaire was 0.719.Results: A total of 3000 questionnaires were distributed, of which 2812 were valid, with a valid response rate of 93.73%. Of the 2812 respondents, 41.18% had seen an automatic external defibrillator (AED), 48.83% had experience of’ cardiopulmonary resuscitation (CPR), and 25.07% of the respondents had experience of’ AEDs. When an accident occurred, 50.50% of residents were willing to attempt rescue, 70.80% were willing to attempt rescue under professional guidance, and 71.23% were willing to attempt rescue after learning BLS techniques. Of the residents who were unwilling to attempt rescue, 32.75% were worried about their lack of ability, 27.91% were concerned about legal issues, 14.01% feared infectious diseases, and 10.35% were unwilling to perform mouth-to-mouth artificial respiration. Age, occupation, education level, and whether they had participated in first aid training were the influencing factors.Conclusion: Residents in Nantong have less knowledge of BLS, and their knowledge of CPR is better than that of AEDs. Residents have a strong willingness to learn BLS. Measures need to be taken to improve their understanding of BLS and their application skills. Residents have high levels of willingness to attempt rescue, but a certain percentage of residents have concerns. Interventions can be made to target the different reasons.Keywords: out-of-hospital cardiac arrest, basic life support, automatic external defibrillator, rescue willing

Jingya Li,1,* Ruizhen Zhao,1,* Xiaoli Li,1 Wenjun Sun,1 Miao Qu,1 Qisheng Tang,1 Xinke Yang,1 Shujing Zhang2 1Third Affiliated Hospital, 2School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Shen-Qi-Jie-Yu-Fang (SJF) is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD). Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg) cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL)-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through the modulation of serum concentrations of IL-1β and IL-6, expressions of IL-1RI, and gp130 in the hippocampus, and CD4+CD25+ Treg cells in peripheral blood. Keywords: postpartum depression, inflammatory cytokines, antidepressant drugs, Chinese herbal medicine, shenqi jieyu fang, animal model

Wenjie Sun,1,2,* Ding Qu,1,* Yihua Ma,1 Yan Chen,1,2 Congyan Liu,1 Jing Zhou11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2Department of Pharmaceutics, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workAbstract: Silver nanoparticles (AgNPs) are widely used as antibacterial products in various fields. Recent studies have suggested that AgNPs need an appropriate stabilizer to improve their stability. Some antibacterial traditional Chinese medicines (TCMs) contain various reductive components, which can not only stabilize AgNPs but also enhance their antimicrobial activity. In this study, we developed a series of novel AgNPs using a TCM extract as a stabilizer, reducing agent, and antimicrobial agent (TCM-AgNPs). A storage stability investigation of the TCM-AgNPs suggested a significant improvement when compared with bare AgNPs. Further, conjugation of TCMs onto the AgNP surface resulted in stronger antimicrobial potency on antibacterial evaluation using Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus with minimum inhibitory concentration 50% (MIC50) ratios (and minimum bactericidal concentration 90% [MBC90] ratios) of AgNPs to respective TCM-AgNPs as assessment indices. Among these, P. cuspidatum Sieb. et-conjugated AgNPs (P.C.-AgNPs) had the advantage of a combination of TCMs and AgNPs and was studied in detail with regard to its synthesis and characterization. The extraction time, reaction temperature, and concentrations of AgNO3 and Polygonum cuspidatum Sieb. et extract were critical factors in the preparation of P.C.-AgNPs. Further, the results of X-ray diffraction and Fourier transform infrared spectroscopy indicated successful preparation of P.C.-AgNPs. In representative studies, P.C.-AgNPs showed a well-defined spherical shape, a homogeneous small particle size (36.78 nm), a narrow polydispersity index (0.105), and a highly negative zeta potential (-23.6 mV) on transmission electron microscopy and dynamic light scattering. These results indicate that TCM-AgNPs have a potential role as antibacterial agents in the clinic setting.Keywords: traditional Chinese medicine, extract, silver nanoparticles, stability, antibacterial, Polygonum cuspidatum Sieb. et

A cylindrical ingot was produced by means of centrifugal casting using 20 vol.% SiCp/Al composite melt. The melt which was fabricated by double stir-casting method, consisting of three different sizes of SiC particles. SiCp/Al composites were characterized by optical microscope (OM), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD) techniques. The results showed that SiC particles in the 20 vol.% SiCp/Al composite melt migrated towards the outer periphery of the cylindrical ingot under centrifugal force. High reinforcement content SiCp/Al composites were obtained in a zone near the outer periphery of the cylindrical ingot, and the volume fraction of SiC particles reached up to 55%. The thermal expansion test was performed, and the coefficient of thermal expansion (CTE) of the 55 vol.% SiCp/Al composites was found to be 9.9 × 10−6/°C, which was lower than the predicted value based on Kerner’s model and that of 60 vol.% SiCp/Al composites fabricated by conventional processing techniques. This article presented an approach for producing high reinforcement content SiCp/Al composites. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine. METHODS: The liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition. RESULTS: The ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05). CONCLUSION: YCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4). [ABSTRACT FROM AUTHOR]

Marine dinoflagellates are increasingly affected by ongoing global climate changes. While understanding of their physiological and molecular responses to individual stressors anticipated in the future ocean has improved, their responses to multiple concurrent stressors remain poorly understood. Here, we investigated the individual and combined effects of elevated temperature (26 °C relative to 22 °C), increased pCO 2 (1000 μatm relative to 400 μatm), and high nitrogen: phosphorus ratio (180:1 relative to 40:1) on a harmful algal bloom-causing dinoflagellate Prorocentrum obtusidens under short-term (28 days) exposure. Elevated temperature was the most dominant stressor affecting P. obtusidens at physiological and transcriptomic levels. It significantly increased cell growth rate and maximum photosynthetic efficiency (Fv/Fm), but reduced chlorophyll a, particulate organic carbon, particulate organic nitrogen, and particulate organic phosphorus. Elevated temperature also interacted with other stressors to produce synergistic positive effects on cell growth and Fv/Fm. Transcriptomic analysis indicated that elevated temperature promoted energy production by enhancing glycolysis, tricarboxylic acid cycle, and nitrogen and carbon assimilation, which supported rapid cell growth but reduced material storage. Increased pCO 2 enhanced the expression of genes involved in ionic acid-base regulation and oxidative stress resistance, whereas a high N:P ratio inhibited photosynthesis, compromising cell viability, although the effect was alleviated by elevated temperature. The combined effect of these multiple stressors resulted in increased energy metabolism and up-regulation of material-synthesis pathways compared to the effect caused by elevated temperature alone. Our results underscore ocean warming as the predominant stressor for dinoflagellates and highlight the complex, synergistic effects of multi-stressors on dinoflagellates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As the most classic photoisomerization system, azobenzene has been widely utilized as a building unit in various photoswitching applications. However, attempts to build azobenzene-based single-molecule photoswitches have met with limited success, giving low on/off ratios. Herein, we demonstrate two designs of azobenzene-based photoresponsive single-molecule junctions, based on mechanically interlocked diazocine and azobenzene-based dynamic anchors, respectively. Molecular conductance measurements using the scanning tunneling microscope breaking junction (STMBJ) technique revealed dramatic conductance changes upon photoillumination, achieving a high on/off ratio of ∼3.7. Using density functional theory (DFT), we revealed peculiar quantum interference (QI) effects in the diazocine molecular switch, indicating that diazocine is an excellent candidate for molecular photoswitches. The asymmetric azobenzene devices with a dynamic anchor exhibit switching behavior between a fully off state and a highly conductive state associated with the trans / cis conformation transition. The findings of this work not only present the design and development of functional molecular devices based on azobenzene units but also provide insight into the fundamental properties of light-induced quantum interference in azobenzene-based molecular devices.

Background and Purpose: Fear of falling and low physical activity become prevalent in an aged society, but their association with fall risk warrants further investigation., Methods: Our study involved 600 individuals aged 70.8-96.1 years who completed two rounds of community surveys. During the second survey, we analyzed the correlations between fall incidents and a range of factors, including age, sex, gait maneuverability, vision, comorbidity count, depressive symptoms, cognitive function, history of falls, fear of falling, and physical activity level. The chi-square test and univariate and multivariate logistic regression models were used, with further analyses either adjusted for or stratified by the full-factor combinations of fear of falling (with versus without) and low physical activity (low versus moderate-to-high)., Results: Falls exhibited a prevalence rate of 13.8%. A fall risk gradient by the full-factor combinations was observed. Multivariate logistic regression modeling identified independent risk predictors for falls, including the number of comorbidities, depressive symptoms, a history of falls, and fear of falling. Fear of falling and low physical activity presented a synergistic effect to increase the fall risk by two- and one-third times (adjusted odds ratio: 2.35, 95% confidence interval: 1.12-4.91). Depressive symptoms, cognitive impairment, and a history of falls remained as significant risk predictors for older adults with both factors, those with fear of falling only, and those with neither, respectively, when the models were further stratified., Conclusion: Fear of falling and low physical activity presented likely synergism to increase the fall risk. Those older community-dwellers with both risk factors warrant fall prevention resources as a priority over those with either or neither., (© 2024. The Author(s).)

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Fungal α/β-glucans have significant importance in cellular functions including cell wall structure, host-pathogen interactions and energy storage, and wide application in high-profile fields, including food, nutrition, and pharmaceuticals. Fungal species and their growth/developmental stages result in a diversity of glucan contents, structures and bioactivities. Substantial progresses have been made to elucidate the fine structures and functions, and reveal the potential molecular synthesis pathway of fungal α/β-glucans. Herein, we review the current knowledge about the biosynthetic machineries, including: precursor UDP-glucose synthesis, initiation, elongation/termination and remodeling of α/β-glucan chains, and molecular regulation to maximally produce glucans in edible fungi. This review would provide future perspectives to biosynthesize the targeted glucans and reveal the catalytic mechanism of enzymes associated with glucan synthesis, including: UDP-glucose pyrophosphate phosphorylases (UGP), glucan synthases, and glucanosyltransferases in edible fungi.

Tacrolimus capsules contain the drug as the amorphous form. It is well known that drug crystallinity is a risk factor for the performance of amorphous formulations. This study investigated the impact of varying levels of crystalline drug on the pharmacokinetics of tacrolimus following oral dosing of a 5 mg capsule under fasting conditions. Two treatments with percent crystallinity of 20% and 50% were achieved by exposing a marketed generic tacrolimus product to open dish storage conditions of 35 °C and 75% relative humidity (RH) for up to 20 days. Crystallinity was monitored with X-ray powder diffraction. Prograf®, the reference listed drug (RLD), an amorphous generic drug product, and generic drug products containing 20% and 50% crystalline tacrolimus were evaluated. All four treatments were administered to healthy participants in a randomized, single-dose, four-treatment, four-period, four-way crossover study. Blood sampling occurred over 24 h. The amorphous generic tacrolimus product was determined not to be bioequivalent to the RLD. The capsules containing both 20% and 50% crystalline tacrolimus also failed the bioequivalence recommendations when compared to the amorphous generic or to the RLD. Both levels of crystalline tacrolimus resulted in BE failure for both C max and AUC parameters. The impact of tacrolimus crystallization was greater for maximum blood concentration (C max ) values relative to the area-under-the-curve (AUC) values. This study demonstrates that crystalline tacrolimus formed in a marketed generic product and these changes resulted in variable pharmacokinetics which could be of significant clinical concern., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.S.T is an Editorial Board Member of the Journal of Pharmaceutical Sciences and Editor-in-Chief of Molecular Pharmaceutics and was not involved in the editorial review or the decision to publish this article. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the FDA., (Copyright © 2024 American Pharmacists Association. All rights reserved.)

Solid additives have drawn great attention due to their numerous appealing benefits in enhancing the power conversion efficiencies (PCEs) of organic solar cells (OSCs). To date, various strategies have been reported for the selection or design of non-volatile solid additives. However, the lack of a general design/evaluation principles for developing non-volatile solid additives often results in individual solid additives offering only one or two efficiency-boosting attributes. In this work, we propose an integrated omnidirectional strategy for designing non-volatile solid additives. By validating the method on the 4,5,9,10-pyrene diimide (PyDI) system, a novel non-volatile solid additive named PyMC5 was designed. PyMC5 is capable of enhancing device performance by establishing synergistic dual charge transfer channels, forming appropriate interactions with active layer materials, reducing non-radiative voltage loss and optimizing film morphology. Notably, the binary device (PM6 : L8-BO) treated by PyMC5 achieved a PCE over 19.5 %, ranking among the highest reported to date. In addition, the integration of PyMC5 mitigated the degradation process of the devices under photo- and thermal-stress conditions. This work demonstrates an efficient integrated omnidirectional approach for designing non-volatile solid additives, offering a promising avenue for further advancements in OSC development., (© 2024 Wiley-VCH GmbH.)

Sediment accretion (burial) and nutrient enrichment may exert a synergistic influence on the growth and distribution of macrophytes in floodplain wetlands; however, this phenomenon has rarely been examined. In this study, we investigated the effects of sediment accretion and nutrient enrichment on the growth and vegetative propagation of Phalaris arundinacea within a Carex thunbergii stand (one P. arundinacea ramet within 25 C . thunbergii ramets) using a factorial sediment burial (0, 3, and 6 cm) and nutrient addition (low, medium, and high) experimental design. High sediment burial (6 cm) without nutrient addition decreased the aboveground and total biomass of C. thunbergii but did not affect P. arundinacea , indicating that P. arundinacea is more tolerant to sediment burial than C. thunbergii . Moderate sediment burial (3 cm) with nutrient addition enhanced the aboveground and total biomass of P. arundinacea but did not affect C. thunbergii , indicating that P. arundinacea may gain a growth advantage over C. thunbergii under moderate sedimentation. High sediment burial with nutrient addition increased the number of rhizomes and ramets produced by P. arundinacea but did not affect C. thunbergii , indicating that the relative abundance of P. arundinacea may increase within the Carex community under high sedimentation conditions. Based on these results, it can be concluded that an increased sedimentation rate facilitates the invasion of P. arundinacea into Carex grasslands, and this invasion is further enhanced by nutrient enrichment. Therefore, management measures should be taken to reduce the sediment load and nutrient input to prevent Carex grasslands invasion by P. arundinacea and maintain the ecological function of floodplain wetlands., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The reviewer ZD declared a past co-authorship with the author X-SC to the handling editor., (Copyright © 2024 Guo, Zhong, Sun, Song, Liu and Chen.)

Dysregulation of brain homeostasis is associated with neuropsychiatric conditions such as major depressive disorder. However, underlying neural-circuit mechanisms remain not well-understood. We show in mice that chronic restraint stress (CRS) and social defeat stress (SDS) are both associated with disruption of excitation (E)-inhibition (I) balance, with increased E/I ratios, in medial preoptic area (MPOA) circuits, but through affecting different neuronal types. CRS results in elevated activity in glutamatergic neurons, and their suppression mitigates CRS-induced depressive-like behaviors. Paraventricular hypothalamic input to these neurons contributes to induction but not expression of depressive-like behaviors. Their projections to ventral tegmental area and periaqueductal gray/dorsal raphe suppress midbrain dopaminergic and serotonergic activity, respectively, and mediate expression of divergent depressive-like symptoms. By contrast, SDS results in reduced activity of GABAergic neurons, and their activation alleviates SDS-induced depressive-like behaviors. Thus, E/I imbalance with relatively increased excitation in MPOA circuits may be a general mechanism underlying depression caused by different etiological factors., (© 2024. The Author(s).)

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1 -/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3β (Gsk3β) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The early diagnosis and treatment of Heliobacter pylori (H.pylori) gastrointestinal infection provide significant benefits to patients. We constructed a convolutional neural network (CNN) model based on an endoscopic system to diagnose H. pylori infection, and then examined the potential benefit of this model to endoscopists in their diagnosis of H. pylori infection., Materials and Methods: A CNN neural network system for endoscopic diagnosis of H.pylori infection was established by collecting 7377 endoscopic images from 639 patients. The accuracy, sensitivity, and specificity were determined. Then, a randomized controlled study was used to compare the accuracy of diagnosis of H. pylori infection by endoscopists who were assisted or unassisted by this CNN model., Results: The deep CNN model for diagnosis of H. pylori infection had an accuracy of 89.6%, a sensitivity of 90.9%, and a specificity of 88.9%. Relative to the group of endoscopists unassisted by AI, the AI-assisted group had better accuracy (92.8% [194/209; 95%CI: 89.3%, 96.4%] vs. 75.6% [158/209; 95%CI: 69.7%, 81.5%]), sensitivity (91.8% [67/73; 95%CI: 85.3%, 98.2%] vs. 78.6% [44/56; 95%CI: 67.5%, 89.7%]), and specificity (93.4% [127/136; 95%CI: 89.2%, 97.6%] vs. 74.5% [114/153; 95%CI: 67.5%, 81.5%]). All of these differences were statistically significant (P < 0.05)., Conclusion: Our AI-assisted system for diagnosis of H. pylori infection has significant ability for diagnostic, and can improve the accuracy of endoscopists in gastroscopic diagnosis., Trial Registration: This study was approved by the Ethics Committee of Daping Hospital (10/07/2020) (No.89,2020) and was registered with the Chinese Clinical Trial Registration Center (02/09/2020)   ( www.chictr.org.cn ; registration number: ChiCTR2000037801)., (© 2024. The Author(s).)

Skyrmions, a stable topological vectorial textures characteristic with skyrmionic number, hold promise for advanced applications in information storage and transmission. While the dynamic motion control of skyrmions has been realized with various techniques in magnetics and optics, the manipulation of acoustic skyrmion has not been done. Here, the propagation and control of acoustic skyrmion along a chain of metastructures are shown. In coupled acoustic resonators made with Archimedes spiral channel, the skyrmion hybridization is found giving rise to bonding and antibonding skyrmionic modes. Furthermore, it is experimentally observed that the skyrmionic mode of acoustic velocity field distribution can be robustly transferred covering a long distance and almost no distortion of the skyrmion textures in a chain of metastructures, even if a structure defect is introduced in the travel path. The proposed localized acoustic skyrmionic mode coupling and propagating is expected in future applications for manipulating acoustic information storage and transfer., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

After conventional oil recovery operations, more than half of the crude oil still remains in a form, which is difficult to extract. Therefore, exploring and developing new enhanced oil recovery (EOR) technologies have always been priority research in oilfield development. Microbial enhanced oil recovery (MEOR) is a promising tertiary oil recovery technology that has received widespread attention from the global oil industry in recent years due to its environmental friendliness, simplicity of operation, and cost-effectiveness. This review presents the: principle, characteristics, classification, recent development, and applications of MEOR technology. Based on hundreds of field trials conducted worldwide, the microbial strains, nutrient systems, and actual effects used in these technologies are summarized, with an emphasis on the achievements made in the development and application of MEOR in China in recent years. These technical classifications involve: microbial huff and puff recovery (MHPR), microbial flooding recovery (MFR), microbial selective plugging recovery (MSPR), and microbial wax removal and control (MWRC). Most of them have achieved good results, with a success rate of approximately 80%. These successful cases have accumulated into rich experiential indications for the popularization and application of MEOR technology, but there are still important yet uncertain factors that hinder the industrialization of this technology. Finally, based on the extensive research and development of MEOR by the authors, especially in both laboratory and industrial large scales, the main challenges and future perspectives of the industrial application for MEOR are presented.

High concentrations of Na + and NH 4 + in landfill leachate lead to deterioration of bentonite barrier and pose a threat to the environment. This study focused on the pollution interception and permeability characteristics of the bentonite barrier exposed to NaCl and NH 4 Cl solutions. Based on previous findings, salt solution concentrations were established at 74.80, 37.40, 18.70, and 9.4 mmol/L. The bentonite contents in the mixture were set at 0, 5, 10, and 15%. The results indicate that the samples exhibit better interception of NH 4 + compared to Na + . This difference arises from the cation exchange sequence, the size of the hydration radius, and the hydrogen bonding of the two cations. Additionally, the difference in hydration enthalpy between the two cations leads to variations in the swelling of bentonite, resulting in a higher hydraulic conductivity coefficient in NH 4 Cl solution. This study shows that although bentonite barriers have better interception for NH 4 + , they exhibit greater hydraulic conductivity in NH 4 Cl solution, increasing the risk of leachate carrying other contaminants., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY-NC-ND 4.0), which permits copying and redistribution for non-commercial purposes with no derivatives, provided the original work is properly cited (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Objectives: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder often exacerbated by stress, influencing the brain-gut axis (BGA). BGA dysregulation, disrupted intestinal barrier function, altered visceral sensitivity and immune imbalance defects underlying IBS pathogenesis have been emphasized in recent investigations. Phosphoproteomics reveals unique phosphorylation details resulting from environmental stress. Here, we employ phosphoproteomics to explore the molecular mechanisms underlying IBS-like symptoms, mainly focusing on the role of ZO-1 and IL-1RAP phosphorylation. Materials and Methods: Morris water maze (MWM) was used to evaluate memory function for single prolonged stress (SPS). To assess visceral hypersensitivity of IBS-like symptoms, use the Abdominal withdrawal reflex (AWR). Colonic bead expulsion and defecation were used to determine fecal characteristics of the IBS-like symptoms. Then, we applied a phosphoproteomic approach to BGA research to discover the molecular mechanisms underlying the process of visceral hypersensitivity in IBS-like mice following SPS. ZO-1, p-S179-ZO1, IL-1RAP, p-S566-IL-1RAP and GFAP levels in BGA were measured by western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay to validate phosphorylation quantification. Fluorescein isothiocyanate-dextran 4000 and electron-microscopy were performed to observe the structure and function of the intestinal epithelial barrier. Results: The SPS group showed changes in learning and memory ability. SPS exposure affects visceral hypersensitivity, increased fecal water content, and significant diarrheal symptoms. Phosphoproteomic analysis displayed that p-S179-ZO1 and p-S566-IL-1RAP were significantly differentially expressed following SPS. In addition, p-S179-ZO1 was reduced in mice's DRG, colon, small intestine, spinal and hippocampus and intestinal epithelial permeability was increased. GFAP, IL-1β and p-S566-IL-1RAP were also increased at the same levels in the BGA. And IL-1β showed no significant difference was observed in serum. Our findings reveal substantial alterations in ZO-1 and IL-1RAP phosphorylation, correlating with increased epithelial permeability and immune imbalance. Conclusions: Overall, decreased p-S179-ZO1 and increased p-S566-IL-1RAP on the BGA result in changes to tight junction structure, compromising the structure and function of the intestinal epithelial barrier and exacerbating immune imbalance in IBS-like stressed mice., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, has a poor prognosis and limited access to efficient targeted treatments. Chronic unpredictable mild stress (CUMS) is highly risk factor for TNBC occurrence and development. Type X collagen (COL10A1), a crucial protein component of the extracellular matrix, ranks second among all aberrantly expressed genes in TNBC, and it is significantly up-regulated under CUMS. Nevertheless, the impact of CUMS and COL10A1 on TNBC, along with the underlying mechanisms are still unclear. In this research, we studied the effect of CUMS-induced norepinephrine (NE) elevation on TNBC, and uncovered that it notably enhanced TNBC cell proliferation, migration, and invasion in vitro, and also fostering tumor growth and lung metastasis in vivo. Additionally, our investigation found that COL10A1 directly interacted with integrin subunit beta 1 (ITGB1), then activates the downstream PI3K/AKT signaling pathway, thereby promoting TNBC growth and metastasis, while it was reversed by knocking down of COL10A1 or ITGB1. Our study demonstrated that the TNBC could respond to CUMS, and advocate for COL10A1 as a pivotal therapeutic target in TNBC treatment., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Desmopressin acetate (DDAVP) and behavioral interventions (BI) are cornerstone treatments for nocturnal enuresis (NE), a common pediatric urinary disorder. Despite the growing body of clinical studies on massage therapy for NE, comprehensive evaluations comparing the effectiveness of Tuina with DDAVP or BI are scarce. This study aims to explore the efficacy of Tuina in the management of NE. Methods: A systematic search of international databases was conducted using keywords pertinent to Tuina and NE. The inclusion criteria were limited to randomized controlled trials (RCTs) that evaluated NE treatments utilizing Tuina against DDAVP or BI. This meta-analysis included nine RCTs, comprising a total of 685 children, to assess both complete and partial response rates. Results: Tuina, used as a combination therapy, showed enhanced clinical efficacy and improved long-term outcomes relative to the control group. The therapeutic efficacy of Tuina was not directly associated with the number of acupoints used. Instead, employing between 11 and 20 acupoints appeared to have the most significant effect. Conclusion: The findings of this meta-analysis support the potential of Tuina as an adjunct therapy to enhance the sustained clinical efficacy of traditional treatments for NE. However, Tuina cannot completely replace DDAVP or BI in the management of NE. While this study illuminates some aspects of the effective acupoint combinations, further research is crucial to fully understand how Tuina acupoints contribute to the treatment of NE in children. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=442644, identifier CRD42023442644., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Sun, Wang, Cai and Yu.)

Soil contamination by petroleum, including crude oil from various sources, is increasingly becoming a pressing global environmental concern, necessitating the exploration of innovative and sustainable remediation strategies. The present field-scale study developed a simple, cost-effective microbial remediation process for treating petroleum-contaminated soil. The soil treatment involves adding microbial activators to stimulate indigenous petroleum-degrading microorganisms, thereby enhancing the total petroleum hydrocarbons (TPH) degradation rate. The formulated microbial activator provided a growth-enhancing complex of nitrogen and phosphorus, trace elements, growth factors, biosurfactants, and soil pH regulators. The field trials, involving two 500 m 3 soil samples with the initial TPH content of 5.01% and 2.15%, were reduced to 0.41% and 0.02% in 50 days, respectively, reaching the national standard for cultivated land category II. The treatment period was notably shorter than the commonly used composting and bioaugmentation methods (typically from 8 to 12 weeks). The results indicated that the activator could stimulate the functional microorganisms in the soil and reduce the phytotoxicity of the contaminated soil. After 40 days of treatment, the germination rate of rye seeds increased from 20 to 90%, indicating that the microbial activator could be effectively used for rapid on-site remediation of oil-contaminated soils., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera . A series of genes putatively associated with alpine adaptation (e.g. CBF s, ERF-VII s, and RAD51C ) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica . Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica , indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNL s, prRLP s, and XII RLK s), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1 , DMC1 , and MSH3 ) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood., Methods: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance., Results: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance., Conclusion: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies., (© 2024. The Author(s).)

Background: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat., Results: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens., Conclusion: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture., (© 2024. The Author(s).)

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution., (© 2023. Science China Press.)

Polysaccharides are the main polymers in edible fungi Grifola frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. Recent efforts have well elucidated the fine structures and biological functions of G. frondosa polysaccharides. The recently-rapid developments and increasing availability in fungal genomes also accelerated the better understanding of key genes and pathways involved in biosynthesis of G. frondosa polysaccharides. Herein, we provide a brief overview of G. frondosa polysaccharides and their activities, and comprehensively outline the complex process, genes and proteins corresponding to G. frondosa polysaccharide biosynthesis. The regulation strategies including strain improvement, process optimization and genetic engineering were also summarized for maximum production of G. frondosa polysaccharides. Some remaining unanswered questions in describing the fine synthesis machinery were also pointed out to open up new avenues for answering the structure-activity relationship and improving polysaccharide biosynthesis in G. frondosa. The review hopefully presents a reasonable full picture of activities, biosynthesis, and production regulation of polysaccharide in G. frondosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stimbiotic supplementation may provide an innovative feed additive solution to accelerate the proliferation of beneficial fiber-degrading bacteria in the distal intestine and the utilization of dietary fiber. Optimal utilization of dietary fiber has multiple benefits for gut health and nutrient utilization. This study was conducted to evaluate the late gestation and lactation performance, the plasma, colostrum, and milk immunoglobulin (IgA, IgG, and IgM) concentrations, and the anti-inflammatory and antioxidant biomarkers in plasma of sows fed with or without a stimbiotic during the late gestation and lactation phase. A total of 40 sows were allocated to two treatment groups: control (CT) with no supplementation or 100 mg/kg stimbiotic (VP), with 20 sows per treatment. Sows were fed the treatment diets from d 85 of gestation to d 28 of lactation. In the results, the average daily weight gain of piglets during lactation was greater from sows fed in the VP group compared to that in the CT group ( p < 0.05). The plasma concentrations of IgM at farrowing and IgG at weaning of the sows fed the diet with the stimbiotic supplementation were much higher than those in the CT sows ( p < 0.05), respectively. In addition, the dietary stimbiotic increased the concentrations of IgM in the colostrum and of IgA and IgM in the milk at d 14 of lactation ( p < 0.05). Plasma concentrations of malondialdehyde (MDA) on d 0 and d 28 of lactation tended to be lower in sows fed the VP diets compared with those of the sows fed the CT diets. Thus, our study indicated that stimbiotic supplementation could improve the daily weight gain of piglets and the immune function of sows in lactation.

Volatile organic compounds (VOCs) are produced by plants responding to biotic and abiotic stresses. According to their biosynthetic sources, induced VOCs are divided into three major classes: terpenoids, phenylpropanoid/benzenoid, and fatty acid derivatives. These compounds with specific aroma characteristics importantly contribute to the aroma quality of oolong tea. Shaking and rocking is the crucial procedure for the aroma formation of oolong tea by exerting mechanical damage to fresh tea leaves. Abundant studies have been carried out to investigate the formation mechanisms of VOCs during oolong tea processing in recent years. This review systematically introduces the biosynthesis of VOCs in plants, and the volatile changes due to biotic and abiotic stresses are summarized and expatiated, using oolong tea as an example.

Background: The aging process increases body fat and susceptibility to heat-related illnesses. The relationship between body composition and symptoms associated with exposure to extreme heat among the elderly is unclear. Additionally, the influence of individual adaptive behaviors in mitigating these risks has not been adequately explored., Objectives: This study aimed to evaluate the association between body composition and heat-related symptoms as well as the potential modifying effects of heat adaptation behavior., Methods: The body composition of elderly individuals was measured using bioelectrical impedance analysis. Face-to-face interviews were conducted a year later to determine the heat-related symptoms and adaptive behaviors practiced for the extremely hot days of the previous year. The association between body composition indices and the presence of more than two symptoms was assessed using logistic regression analysis, while stratified analysis and interaction term in models were used to evaluate the effect modifications of adaptive behaviors., Results: Of the 859 participants, 16% reported more than two heat-related symptoms. Increased body fat mass index (fat mass in kg/squared height in meters) was associated with an elevated risk of more heat-related symptoms (odds ratio 1.11, 95% confidence interval 1.02-1.20). Each combination of staying indoors, using an umbrella and hat, and using air conditioning at noon reduced the risk association between body fat and symptoms. For females, a combination of reducing physical activity and staying indoors provided similar protective effect. Surprisingly, bathing more frequently in hot weather with heated instead of non-heated water augmented the risk correlation. Neither fan usage nor window opening displayed protective effects., Conclusions: Elevated body fat levels, indicative of obesity, corresponded with an increased risk of heat-related symptoms. Integrating multiple adaptive behaviors can diminish the negative health impact of body fat on heat-induced symptoms. However, certain commonly adopted practices might not confer expected benefits., (Copyright © 2023. Published by Elsevier GmbH.)

Background: HELLP syndrome, featuring hemolysis, elevated liver enzymes, and thrombocytopenia, is life-threatening disease of pregnancy that triggers comorbidities in both pregnant women and the fetus/newborn. This study provides an updated systematic review and meta-analysis of relevant studies to assess the therapeutic efficacy of corticosteroids in maternal and neonatal outcomes., Methods: Randomized control trials (RCTs) regarding the use of corticosteroids in the HELLP population from three electronic databases, including Ovid MEDLINE, Ovid EMBASE, andCochrane Central Register of Controlled Trials, were searched from database inception to 23 March 202323 March 2023., Results: A total of 485 patients treated with corticosteroids from 7 RCTs were included. Compared to placebo, corticosteroids therapy failed to significantly improve the maternal outcomes regard to maternal morbidity (RR = 1.36, 95%CI [0.45, 4.10]), eclampsia (RR = 1.16, 95%CI [0.76, 1.77]), acute renal failure (RR = 0.71, 95%CI [0.41, 1.22]), pulmonary edema (RR = 0.34, 95%CI [0.10, 1.15]) and oliguria (RR = 1.08, 95%CI [0.75, 1.54]). In addition, pooled data showed that it wasn't significant differences between corticosteroids therapy and placebo regarding neonatal outcomes., Conclusions: This study compared the efficacy of corticosteroids in patients with HELLP syndrome, revealing that corticosteroids did not provide any significant benefit in clinical outcomes for pregnant women and newborns with HELLP. The conclusions of this study must be verified by a larger sample of high-quality RCTs.

The mechanical environment is important for tumorigenesis and progression. Tumor cells can sense mechanical signals by mechanosensitive receptors, and these mechanical signals can be converted to biochemical signals to regulate cell behaviors, such as cell differentiation, proliferation, migration, apoptosis, and drug resistance. Here, we summarized the effects of the mechanical microenvironment on breast cancer cell activity, and mechanotransduction mechanism from cellular microenvironment to cell membrane, and finally to the nucleus, and also relative mechanosensitive proteins, ion channels, and signaling pathways were elaborated, therefore the mechanical signal could be transduced to biochemical or molecular signal. Meanwhile, the mechanical models commonly used for biomechanics study in vitro and some quantitative descriptions were listed. It provided an essential theoretical basis for the occurrence and development of mechanosensitive breast cancer, and also some potential drug targets were proposed to treat such disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Chen-Yan Zhang reports financial support was provided by National Natural Science Foundation of China. Chen-Yan Zhang reports financial support was provided by Shaanxi Provincial Key R&D Program. Chen-Yan Zhang reports financial support was provided by China Postdoctoral Science Foundation. Li Ren reports financial support was provided by Ningbo Natural Science Foundation of China. Da-Chuan Yin reports financial support was provided by Innovation Capability Support Program of Shaanxi. Yan Zhou reports financial support was provided by Undergraduate Training Programs for Innovation and Entrepreneurship., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abuse-deterrent formulations (ADFs) refer to formulation technologies aiming to deter the abuse of prescription drugs by making the dosage forms difficult to manipulate or extract the opioids. Assessments are required to evaluate the performance of the drugs through different routes including injection, ingestion, and insufflation and also when the drugs are manipulated. Chewing is the easiest and most convenient way to manipulate the drugs and deserves investigation. Chewing is one of the most complex bioprocesses, where the ingested materials are subject to periodic tooth crushing, mixed through the tongue, and lubricated and softened by the saliva. Inter- and intra-subject variations in chewing patterns may result in different chewing performances. The purpose of this study is to use a chewing simulator to assess the deterrent properties of tablets made of polyethylene oxide (PEO). The simulator can mimic human molar grinding with variable chewing parameters including molar trajectory, chewing frequency, and saliva flow rate. To investigate the effects of these parameters, the sizes of the chewed tablet particles and the chewing force were measured to evaluate the chewing performance. Thirty-four out of forty tablets were broken into pieces. The results suggested that the simulator can chew the tablets into smaller particles and that the molar trajectory and saliva flow rate had significant effect on reducing the size of the particles by analysis of variance (ANOVA) while the effect of chewing frequency was not clear. Additionally, chewing force can work as an indicator of the chewing performance., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, An, Zhang, Zhao, Sun, Yang, Kang, Jiang, Ji and Lian.)

Background: Current guidelines stress the importance of exercise, especially multicomponent exercise to older adults with chronic conditions., Aim: To critically synthesise evidence that evaluates the effects of multicomponent exercise on quality of life, depression and anxiety after stroke., Design: Systematic review and meta-analysis followed the PRISMA 2020 statement., Methods: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL and PsycINFO from inception to 12 June 2023 was performed. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Meta-analyses were conducted using Review Manager 5.4 and narrative syntheses were adopted whenever meta-analysis was inappropriate. The overall certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Results: Of 15,351 records identified, nine were eligible and data were available for seven randomised controlled trials, three of which were identified as having a high risk of bias, one as low risk, and five as having some concerns. Subgroup pooled analyses indicated that multicomponent exercise engaged in longer exercise sessions (>60 min) was effective in improving quality of life immediately post-intervention and through 3-6 months post-intervention. However, multicomponent exercise did not significantly affect depression and anxiety., Conclusions: Multicomponent exercise with longer duration of exercise sessions has promising effects on both short- to medium-term quality of life among stroke survivors., Patient or Public Contribution: This does not apply to our work as it is a review paper., Relevance to Clinical Practice: Healthcare providers could consider encouraging the patients to participate in multicomponent exercise sessions for more than 60 min. It is important to note that stroke survivors should be supervised by trained personnel at the beginning of the training., Registration: The protocol was registered on PROSPERO., (© 2023 John Wiley & Sons Ltd.)