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Abstract We reported transport diagrams of self-assembled germanium (Ge) double quantum-dots (DQDs) using direct current measurement under illumination at wavelength (λ) of 850 nm and at the base temperature of 4.5 K. Ge DQDs with a coupling-barrier of Si, tunneling-barriers of Si3N4, and self-aligned p+-Si reservoirs were fabricated in a self-organized CMOS approach. Charge transport through the Ge-DQDs is facilitated by photon-assisted tunneling. Characteristic gate-controlled hexagonal-shaped cells over a wide range of hole occupancy are acquired thanks to hard-wall confinement. Large dimensions (ΔV G > 200 mV) of hexagonal-shaped cells are favored for the operation of charge states, indicating that our Ge DQDs system is less susceptible to shot noises arising from external voltage sources. Estimated intra-QD and inter-QD charging energies are E C,R/E C,L = 48.9 meV/42.7 meV and E Cm = 7.8 meV, respectively.

Abstract To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60–90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30–60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively.

Abstract To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P

Abstract Background Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. Methods PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China’s two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. Results A total of 39 trials with 2959 patients were included (range of mean ages, 58.79–77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. Conclusions The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. Trial registration PROSPERO registry number. CRD42022355363.

Abstract With business process optimization, technological advancement, equipment capability enhancement, and other means, the Railway Passenger Service Department in China is consistently working to improve the efficiency and convenience of passenger entry and exit procedures at railway stations. Concerning passengers’ checkout, not only conventional identification approaches based on manual control, identification card, and magnetic thermal paper ticket are supported, but also a recent contactless identification process based on face recognition is applied in some stations. To further improve the contactless identification ability for checkout, an advanced contactless checkout process based on gait-augmented face recognition is innovatively put forward, in which a weakly-supervised body segmentation network named Dwsegnet and an improved GaitSet model are proposed. Through comparison with various models, the effectiveness of both Dwsegnet and the improved GaitSet is validated. Specifically, the contactless identification rate of gait-augmented face recognition is improved by 2.31% when compared to single-modal face recognition, which demonstrates the superiority of the proposed process.

Abstract Background Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. Methods We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. Results We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. Conclusions Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.

Abstract Traditionally, lactate has been considered a ‘waste product’ of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation (‘lactate clock’) in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.

Abstract Background G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. Methods The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. Results Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes’ transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy’s efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. Conclusion This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy. Graphical Abstract

Abstract Mucopolysaccharidoses (MPSs) are caused by a deficiency in the enzymes needed to degrade glycosaminoglycans (GAGs) in the lysosome. The storage of GAGs leads to the involvement of several systems and even to the death of the patient. In recent years, an increasing number of therapies have increased the treatment options available to patients. Early treatment is beneficial in improving the prognosis, but children with MPSs are often delayed in their diagnosis. Therefore, there is an urgent need to develop a method for early screening and diagnosis of the disease. Tandem mass spectrometry (MS/MS) is an analytical method that can detect multiple substrates or enzymes simultaneously. GAGs are reliable markers of MPSs. MS/MS can be used to screen children at an early stage of the disease, to improve prognosis by treating them before symptoms appear, to evaluate the effectiveness of treatment, and for metabolomic analysis or to find suitable biomarkers. In the future, MS/MS could be used to further identify suitable biomarkers for MPSs for early diagnosis and to detect efficacy.

Abstract Without intervention, a considerable proportion of patients with metabolism‐associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism‐associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1 + Ccr2 + monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1 + Ccr2 + Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1 + Ccr2 + Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

Abstract Background Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. Methods We selected 8115 patients with osteoporosis (T-score ≤ − 2.5) and 55,942 healthy individuals (T-score > − 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient’s cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. Results The GBA1 gene variant rs11264345 was significantly associated [P

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Daylily (Hemerocallis citrina) is a perennial herb of the genus Hemerocallis of Liliaceae. It is also an economically important crop and is widely cultivated. Daylily has nutritional, medicinal and ornamental values. The research literature shows that daylily is a high-quality food raw material rich in soluble sugars, ascorbic acid, flavonoids, dietary fiber, carotenoids, mineral elements, polyphenols and other nutrients, which are effective in clearing heat and diuresis, resolving bruises and stopping bleeding, strengthening the stomach and brain, and reducing serum cholesterol levels. This article reviews the main nutrients of daylily and summarizes the drying process of daylily. In addition, due to the existence of active ingredients, daylily also has a variety of biological activities that are beneficial to human health. This article also highlights the nutritional quality of daylily, the research progress of dried vegetable rehydration technology and dried daylily. In the end, the undeveloped molecular mechanism and functional research status of daylily worldwide are introduced in order to provide reference for the nutritional quality research and dried processing industry of daylily.

Abstract This study aimed to assess the impact of light perception presence or absence on visual function recovery in patients with traumatic optic neuropathy (TON). A retrospective analysis was conducted on the clinical data of 206 TON patients. Based on the presence or absence of light perception after injury, patients were categorized into a light perception group and a non-light perception group. A comparison was made between the two groups regarding visual acuity recovery before and after treatment. The non-light perception group comprised 63 patients, with a treatment effectiveness rate of 39.68%. The light perception group consisted of 143 patients, with a treatment effectiveness rate of 74.83%. The difference between the two groups was statistically significant (χ2 = 23.464, P

Abstract Aim The transition from medical students to competent physicians requires comprehensive training during residency programs. In China, resident students typically undergo 2- or 3-year training programs. While they learn from patient interactions under the guidance of experienced doctors, integrating theoretical knowledge from textbooks into practical cases remains a challenge. This study aimed to explore the impact of medical interns acting as peer-students on the knowledge mastery of resident students. Method The participants of this study consisted of resident students specializing in respiratory medicine at the Second Affiliated Hospital of Zhejiang University, School of Medicine. Resident students were given the opportunity to volunteer as peer-teachers for medical interns in the respiratory department. Those who chose to instruct interns were automatically placed into the test group, while those who opted not to partake in intern instruction formed the control group. In their role as peer-teachers, resident students assumed the responsibility of guiding interns in patient management throughout the entire continuum, spanning from initial engagement to discharge, a commitment that extended over a minimum period of 2 weeks. The resident students' academic performance was evaluated through a departmental examination consisting of 50 multiple-choice questions, which was administered upon completing their rotation. Statistical analysis was performed to assess the impact of peer-teaching on the resident students’ performance. Results Between January 2023 and June 2023, a total of 158 resident students completed their rotation in the respiratory department. Among them, 40 resident students willingly took on the responsibility of instructing medical interns, while 118 resident students did not participate in intern teaching. With a "one-to-one" teaching policy in place, the overall satisfaction rate of the interns was an impressive 95.35%. Pre-rotation test scores for the test group averaged 81.66 ± 8.325 (Mean ± SD) and the control group averaged 81.66 ± 8.002, without significance. The departmental examination scores of the test group averaged 85.60 ± 7.886, while the control group scored an average of 82.25 ± 8.292, with a statistically significant difference (p = 0.027). Conclusion In conclusion, our study underscores the positive influence of peer-teaching on the knowledge mastery of resident students.

Abstract Evidence regarding the association between dietary niacin intake and chronic obstructive pulmonary disease (COPD) is limited. Our study investigates the relationship between dietary niacin intake and the prevalance and incidence of COPD in the adult population of the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Data on niacin intake were extracted through dietary intake interviews. COPD diagnoses were based on lung function, medical history, and medication usage. We analyzed the association between niacin consumption and COPD using multiple logistic regression and restricted cubic spline models. The study included 7055 adult participants, divided into COPD (n = 243; 3.44%) and non-COPD (n = 6812; 96.56%) groups. Those with COPD had lower average niacin intake (21.39 ± 0.62 mg/day) compared to the non-COPD group (25.29 ± 0.23 mg/day, p

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

Objective: The aim of this study was to examine the cervical cancer screening practices among women residing in Lingang New District of Shanghai. Moreover, the study aimed to delve into the characteristics of HPV infection and cervical lesions in older women (≥60 years old), seeking for more effective method for cervical cancer screening. Methods: This is a cross-sectional study enrolled women who were referred to colposcopy and cervical histological examination due to abnormal cytology or HPV tests from Shanghai Sixth People's Hospital between January 2018 and December 2022. Results: A total of 1,931 women (mean age: 41.8 ± 12.5, range: 18–88 years old) were enrolled, 119 individuals aged ≥ 60 and 1732 aged

Background Severe pneumonia (SP) stands as one of the most prevalent critical illnesses encountered in clinical practice, characterised by its rapid onset and progression, numerous complications and elevated mortality rates. While modern medical interventions primarily focus on symptomatic management such as anti-infective therapy and mechanical ventilation, challenges including high drug resistance and suboptimal therapeutic outcomes for certain patients persist. Dry cupping as an ancient practice with over a millennium of clinical use in China is renowned for its convenience and perceived clinical efficacy in various illnesses. Nevertheless, the lack of well-designed studies assessing its effects remains a notable gap in the literature. This protocol describes a placebo-controlled, randomised, single-blind study to evaluate the efficacy and safety of dry cupping as an adjuvant treatment for SP.Methods and analysis 66 patients diagnosed with SP, aged 18–80 years, will be randomly divided into two groups: intervention group, receiving 10 times of dry cupping treatment; control group, receiving placebo dry cupping therapy. Both applications are used in bilateral Fei Shu (BL13), Pi Shu (BL21) and Shen Shu (BL22) cupping. The application will be conducted once a day for 10 days. Participants will be assessed before treatment (D0), after the first intervention (D1), after the fifth intervention (D5) and after treatment ended (D10). The assessments include blood oxygen saturation, respiratory rate, traditional Chinese medicine symptom score, inflammatory response, mechanical ventilation time and oxygen condition.Ethics and dissemination This protocol has been approved by the Ethics Committee of Shanghai Seventh People’s Hospital (2023-7th-HIBR-070). The results of the study will be disseminated to participants through social networks and will be submitted to a peer-reviewed journal and scientific meetings.Trial registration number ChiCTR2300076958.

The microbial communities, inhabiting around and in plant roots, are largely influenced by the compartment effect, and in turn, promote the growth and stress resistance of the plant. However, how soil microbes are selected to the rhizosphere, and further into the roots is still not well understood. Here, we profiled the fungal, bacterial communities and their interactions in the bulk soils, rhizosphere soils and roots of eleven stress-resistant plant species after six months of growth. The results showed that the root selection (from the rhizosphere soils to the roots) was stronger than the rhizosphere selection (from the bulk soils to the rhizosphere soils) in: (1) filtering stricter on the fungal (28.5% to 40.1%) and bacterial (48.9% to 68.1%) amplicon sequence variants (ASVs), (2) depleting more shared fungal (290 to 56) and bacterial (691 to 2) ASVs measured by relative abundance, and (3) increasing the significant fungi-bacteria crosskingdom correlations (142 to 110). In addition, the root selection, but not the rhizosphere selection, significantly increased the fungi to bacteria ratios (f:b) of the observed species and shannon diversity index, indicating unbalanced effects to the fungal and bacteria communities exerted by the root selection. Based on the results of network analysis, the unbalanced root selection effects were associated with increased numbers of negative interaction (140 to 99) and crosskingdom interaction (123 to 92), suggesting the root selection intensifies the negative fungi-bacteria interactions in the roots. Our findings provide insights into the complexity of crosskingdom interactions and improve the understanding of microbiome assembly in the rhizosphere and roots.

Introduction Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found.Methods/design The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35–45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases.Ethics and dissemination The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300072472).

Abstract Background Androgenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis. Methods The lifespan of Caenorhabditis elegans was measured to examine the capacity of Derinat to oppose the oxidative stress induced-aging process, which drives the hair cycle from anagen to catagen phase. The experiments that used BALB/c-nu and C57BL/6 mice determined the effects of Derinat on hair cycle and oxidative stress in skin. To further apply Derinat to clinical study, the resulting relationship between AGA pathogenesis and TRPCs-regulated oxidative stress was confirmed using the bioinformatics approach. We consequently used the parameters of hair density, hair diameter, hair recovery and quality of life index to evaluate the effect of Derinat treatment on AGA subjects. Results Derinat restrained the oxidative stress induced-aging process sufficiently to extend the lifespan of worms. Derinat also changed the hair growth patterns of mice by maintenance of the hair cycle at the anagen phase. This efficacy was due to reduction of TRPCs-mediated ROS accumulation. Because the bioinformatics analysis found that AGA pathogenesis is associated with TRPCs-regulated oxidative stress and inflammation, treatment with Derinat in AGA subjects increased positive outcomes of oral medication while mitigating the impairment of AGA subjects’ quality of life. Conclusions Derinat restrains AGA pathogenesis and may provide a new therapeutic approach for treating AGA. ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022. Trial registration ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022

Abstract Hepatitis B protein x (HBx) has been reported to promote tumorigenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but the mechanism awaits further investigation. In this study, we found that cFAM210A (a circular RNA derived from the third exon of transcript NM_001098801 of the FAM210A gene; CircBase ID: hsa_circ_0003979) can be silenced by HBx. cFAM210A expression was downregulated and negatively correlated with tumorigenesis in patients with HBV-related HCC. Furthermore, cFAM210A reduced the proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, HBx increased the N6-methyladenosine (m6A) level of cFAM210A by promoting the expression of RBM15 (an m6A methyltransferase), thus inducing the degradation of cFAM210A via the YTHDF2-HRSP12-RNase P/MRP pathway. cFAM210A bound to YBX1 and inhibited its phosphorylation, suppressing its transactivation function toward MET. These findings suggest the important role of circular RNAs in HBx-induced hepatocarcinogenesis and identify cFAM210A a potential target in the prevention and treatment of HBV-related HCC.

Objective To screen the potential key genes associated with colon cancer(CC) by bioinformatics analysis based on Gene Expression Omnibus (GEO) database, and verify them through in vitro experiments to explore potential colon cancer molecular markers. Methods The human CC data sets GSE10950 and GSE74602 were obtained from GEO database. The differentially expressed genes (DEGs) in colon cancer and adjacent tissues were screened by GEO2R tool and Venn diagram software. DEGs were used to perform by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The Protein-Protein Interaction (PPI) network of DEGs was constructed by STRING database, then the key genes were screened with Cytoscape software. GEPIA database was used to validate expression and prognostic value of key genes. Finally, the functions of key genes were further verified by cell transfection and CCK8 assays. Results 515 DEGs were obtained from two datasets, of which 223 were up-regulated and 292 were down-regulated. GO enrichment analysis showed that up-regulated DEGs were mainly involved in negative regulation of cell cycle, transcriptional control. KEGG signaling pathways analysis showed that up-regulated DEGs were mainly enriched in cell cycle signaling pathways. A total of 33 hub genes were screened through the PPI. UCLCAN analysis was implemented and 7 of 33 genes were relative to lower survival rate of CC patients. The expression levels of 7 genes by GEPIA analysis (P＜0.05).It was verified by GEPIA database that CCNB1,CCNA2,CDC20,CDKN3,DLGAP5,HMMR and NCAPG were highly expressed in colon cancer tissues. KEGG pathway enrichment and found that three critical genes (CCNB1, CDC20 and CCNA2) enriched in cell cycle pathway. The inhibition of CCNB1,CDC20 or CCNA2 significantly promoted proliferation of colon cancer cells. Conclusions A total of 7 key genes were identified to be involved in the occurrence of CC. The expression of CCNB1,CDC20 and CCNA2 is potentially related to the poor prognosis in CC, which may be potential targets of clinical treatment and prognostic markers for CC patients.

Research on facial micro-expression analysis has been going on for decades. Micro-expression can reflect the true emotions of individuals, and it has important application value in assisting auxiliary diagnosis and disease monitoring of mental disorders. In recent years, the development of artificial intelligence and big data technology has made the automatic recognition of micro-expressions possible, which will make micro-expression analysis more convenient and more widely used. This paper reviews the development of facial micro-expression analysis and its application in forensic psychiatry, to look into further application prospects and development direction.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Nitrogen (N) addition is a simple and effective field management approach to enhancing plant productivity. Nonetheless, the regulatory mechanisms governing nitrogen concentrations and their effect on soil enzyme activity, nutrient levels, and seed yield in the Festuca kirilowii seed field have yet to be elucidated. Therefore, this study sought to investigate the effect of N fertilizer application on soil enzyme activities, soil nutrients, and seed yield of F. kirilowii Steud cv. Huanhu, the only domesticated variety in the Festuca genus of the Poaceae family, was investigated based on two-year field experiments in the Qinghai–Tibet Plateau (QTP). Results showed that N input significantly affected soil nutrients (potential of hydrogen, total nitrogen, organic matter, and total phosphorus). In addition, soil enzyme activities (urease, catalase, sucrase, and nitrate reductase) significantly increased in response to varying N concentrations, inducing changes in soil nutrient contents. Introducing N improved both seed yield and yield components (number of tillers and number of fertile tillers). These findings suggest that the introduction of different concentrations of N fertilizers can stimulate soil enzyme activity, thus hastening nutrient conversion and increasing seed yield. The exhaustive evaluation of the membership function showed that the optimal N fertilizer treatment was N4 (75 kg·hm−2) for both 2022 and 2023. This finding provides a practical recommendation for improving the seed production of F. kirilowii in QTP.

Abstract Background Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan. Materials and methods Data from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998, and April 2022, in these two hospitals for review. A total of 42 individuals were included, six of whom were diagnosed by NBS. Results Our cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis, than that reported worldwide. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed during the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT was shown to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms in GD3 patients progressed despite ERT intervention. Conclusion ERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.

Abstract Liver sinusoidal endothelial cells (LSECs) play a pivotal role in maintaining liver homeostasis and influencing the pathological processes of various liver diseases. However, neither LSEC-specific hallmark genes nor a LSEC promoter-driven Cre mouse line has been introduced before, which largely restricts the study of liver diseases with vascular disorders. To explore LSEC-specific hallmark genes, we compared the top 50 marker genes between liver endothelial cells (ECs) and liver capillary ECs and identified 18 overlapping genes. After excluding globally expressed genes and those with low expression percentages, we narrowed our focus to two final candidates: Oit3 and Dnase1l3. Through single-cell RNA sequencing (scRNA-seq) and analysis of the NCBI database, we confirmed the extrahepatic expression of Dnase1l3. The paired-cell sequencing data further demonstrated that Oit3 was predominantly expressed in the midlobular liver ECs. Subsequently, we constructed inducible Oit3-CreERT2 transgenic mice, which were further crossed with ROSA26-tdTomato mice. Microscopy validated that the established Oit3-CreERT2-tdTomato mice exhibited significant fluorescence in the liver rather than in other organs. The staining analysis confirmed the colocalization of tdTomato and EC markers. Ex-vivo experiments further confirmed that isolated tdTomato+ cells exhibited well-differentiated fenestrae and highly expressed EC markers, confirming their identity as LSECs. Overall, Oit3 is a promising hallmark gene for tracing LSECs. The establishment of Oit3-CreERT2-tdTomato mice provides a valuable model for studying the complexities of LSECs in liver diseases.

Abstract We reported exciton binding-energy determination using tunneling-current spectroscopy of Germanium (Ge) quantum dot (QD) single-hole transistors (SHTs) operating in the few-hole regime, under 405–1550 nm wavelength (λ) illumination. When the photon energy is smaller than the bandgap energy (1.46 eV) of a 20 nm Ge QD (for instance, λ = 1310 nm and 1550 nm illuminations), there is no change in the peak voltages of tunneling current spectroscopy even when the irradiation power density reaches as high as 10 µW/µm2. In contrast, a considerable shift in the first hole-tunneling current peak towards positive VG is induced (ΔVG ≈ 0.08 V at 0.33 nW/µm2 and 0.15 V at 1.4 nW/µm2) and even additional photocurrent peaks are created at higher positive VG values (ΔVG ≈ 0.2 V at 10 nW/µm2 irradiation) by illumination at λ = 850 nm (where the photon energy matches the bandgap energy of the 20 nm Ge QD). These experimental observations were further strengthened when Ge-QD SHTs were illuminated by λ = 405 nm lasers at much lower optical-power conditions. The newly-photogenerated current peaks are attributed to the contribution of exciton, biexciton, and positive trion complexes. Furthermore, the exciton binding energy can be determined by analyzing the tunneling current spectra.

Abstract The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case–control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on ‘TERT rs2736100 polymorphism and LC susceptibility’ in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors.

A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli. The N fragment belongs to the C-terminal domain whereas the S2 fragment spans the fibre structure in the post-fusion conformation of the spike protein. The resultant protein, named S2NDH, was able to form spherical particles of 10 nm, which forms aggregates upon mixture with the CpG ODN-39M. Both preparations were recognized by positive COVID-19 human sera. The S2NDH + ODN-39M formulation administered by the intranasal route resulted highly immunogenic in Balb/c mice. It induced cross-reactive anti-N humoral immunity in both sera and bronchoalveolar fluids, under a Th1 pattern. The cell-mediated immunity (CMI) was also broad, with positive response even against the N protein of SARS-CoV-1. However, neither neutralizing antibodies (NAb) nor CMI against the S2 region were obtained. As alternative, the RBD protein was included in the formulation as inducer of NAb. Upon evaluation in mice by the intranasal route, a clear adjuvant effect was detected for the S2NDH + ODN-39M preparation over RBD. High levels of NAb were induced against SARS-CoV-2 and SARS-CoV-1. The bivalent formulation S2NDH + ODN-39M + RBD, administered by the intranasal route, constitutes an attractive proposal as booster vaccine of sarbecovirus scope.

Abstract T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Abstract Uterine clear cell carcinoma (UCCC) is a relatively rare endometrial cancer. There is limited information on its prognosis. This study aimed to develop a predictive model predicting the cancer-specific survival (CSS) of UCCC patients based on data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. A total of 2329 patients initially diagnosed with UCCC were included in this study. Patients were randomized into training and validation cohorts (7:3). Multivariate Cox regression analysis identified that age, tumor size, SEER stage, surgery, number of lymph nodes detected, lymph node metastasis, radiotherapy and chemotherapy were independent prognostic factors for CSS. Based on these factors, a nomogram for predicting the prognosis of UCCC patients was constructed. The nomogram was validated using concordance index (C-index), calibration curves, and decision curve analyses (DCA). The C-index of the nomograms in the training and validation sets are 0.778 and 0.765, respectively. Calibration curves showed good consistency of CSS between actual observations and nomogram predictions, and DCA showed that the nomogram has great clinical utility. In conclusion, a prognostic nomogram was firstly established for predicting the CSS of UCCC patients, which can help clinicians make personalized prognostic predictions and provide accurate treatment recommendations.

Abstract The origins of composite tiles, one of the oldest forms of roofing, are still unclear. This study is based on a set of over 5000 clay tile fragments excavated from a single context in the Qiaocun site on the Chinese Loess Plateau, dated to ~ 2400–2200 BCE (Early Longshan Period). By combining morphological measurement statistics, 3D modeling, computer-based simulations, and reference to historical and archaeological records, we reconstruct the earliest known composite-tile roofing techniques and demonstrate that tile production was under a low-level standardization, with manual control forming a key agent during the roofing process. The quantitative study of the composite roof tiles from Qiaocun was then placed in its archaeological context and compared with other sites on the Loess Plateau. It was found that tile-roofed buildings were, by necessity, community projects. Such structures served as nodes in larger social communication networks; additionally, their appearance was linked to intensified social complexity in public affairs during the Longshan Period. The invention of clay tiles was associated with the inception of thick rammed-earth walls which had sufficient strength to serve as load-bearing structures for heavy tiled roofs. The roof tiles excavated from Qiaocun site indicate that the Loess Plateau was a key center for the origin and spread of composite tiles and related roofing and construction methods, suggesting a Longshan–Western Zhou tradition of roofing techniques in East Asia.

AbstractBackground Interleukin (IL)-6 is a pro-inflammatory cytokine that plays an important role in preterm birth (PTB), Several meta-analyses investigated the association between IL-6 and PTB, but definitive conclusion has not yet been achieved. This updated meta-analysis aimed to ascertain the association between IL-6 and PTB by examining IL-6 levels in both normal birth and PTB groups.Material and methods Prospective cohort studies were retrieved in PubMed, Embase, and the Cochrane library from their inception until 18 February 2020. The primary outcome was the association between IL-6 and PTB, and secondary outcomes were the association between IL-6 and spontaneous PTB.Results Nine studies involving 1904 patients were included. Overall, IL-6 from different sample types (maternal blood, amniotic fluid and cervicovaginal fluid) was associated with PTB (standard mean difference [SMD]: 0.86, 95% confidence interval [CI]: 0.32 to 1.39, p

AbstractObjective To investigate the differences in the viscoelastic properties between normal trapezius muscles and those in patients with trapezius myofascial pain syndrome (MPS) using real-time shear-wave elastography (SWE).Materials and Methods This study included 31 patients with trapezius MPS and 31 volunteers. Sixty-one trapezius muscles (41 and 20 on the affected and non-affected side, respectively) of patients with MPS and 62 normal trapezius muscles in volunteers were assessed. Conventional ultrasonic parameters, including skeletal muscle thickness, resistance index (RI), and mean shear wave velocity (SWVmean) of trapezius muscles, were obtained in the seated position with the shoulders and neck relaxed. The daily neck leaning time (unit:hours) of all participants was obtained using a questionnaire.Results Ultrasound showed no statistically significant differences in thickness or RI of the trapezius muscles of the affected and non-affected sides in MPS patients versus normal trapezius muscles (p = 0.976 and 0.106, respectively). In contrast, the SWVmean of trapezius muscles in patients with MPS was significantly higher than that of normal trapezius muscles in both the affected and non-affected sides (4.41 ± 1.02 m/s vs. 3.35 ± 0.79 m/s, p

Abstract Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single‐cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti‐inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the change of the epigenetic regulator enhancer of zeste homolog2 (EZH2) accompanied with the emergence of hepatic senescent cells while liver fibrosis regressed. Blocking EZH2 signaling by EPZ6438 reduced hepatic senescent cells and macrophages, decelerating liver fibrosis regression. Moreover, the promoter region of EZH2 was transcriptionally suppressed by Notch‐Hes1 (hairy and enhancer of split 1) signaling. Disruption of Notch in macrophages using Lyz2 (lysozyme 2) Cre‐RBP‐J (recombination signal binding protein Jκ) f/f transgenic mice, enhanced hepatic cellular senescence, and facilitated fibrosis regression by upregulating EZH2 and blocking EZH2 abrogated the above effects caused by Notch deficiency. Ultimately, adopting Notch inhibitor Ly3039478 or exosome‐mediated RBP‐J decoy oligodeoxynucleotides accelerated liver fibrosis regression by augmenting hepatic cellular senescence.

Abstract Background This study explored the specialty preferences of China-educated international medical students (IMSs), who are mainly from low- and middle-income countries (LMICs) and constitute a potential medical workforce both for their home countries and foreign countries, and the influence of migration intentions on their specialty preferences. Methods A cross-sectional, questionnaire-based survey was conducted at 5 universities in China. The questionnaire link was distributed electronically among the IMSs at the 5 universities via emails. The questionnaire enquired IMSs’ demographic information, migration intentions and their specialty preferences. The Chi-square test was applied to determine the influence of the respondent’s gender, intention to practise in the home country and intention to practise in a high-income country on their specialty choices. The Chi-square test was also applied to determine the influence of the respondent’s gender, year of study and country of origin on their preferences for generalist-orientated or non-generalist orientated specialties. Results Altogether, 452 IMSs returned their responses, yielding a response rate of 64.1%. Approximately half of the IMSs planned to not return to their home country. The most selected specialty was general surgery and the least selected specialty was physical medicine and rehabilitation. No significant differences were evident in most specialty preferences between those who intended to return home and those who intended to stay abroad. Among the IMSs having intentions of returning to their home country, male students tended to choose a generalist-orientated specialty, while female students tended to choose a non-generalist-orientated specialty. Conclusion China-educated IMSs could play important roles in the primary care services as well as other shortage specialties both for their home countries or foreign countries. Therefore, it is recommended that governments in these countries plan migration and recruitment policies that cater for these studying-abroad medical students from LMICs, especially in this challenging time during the COVID-19 pandemic.

CD8+CD25+Treg can inhibit immune response and induce immune tolerance. This article reviews the changes and underlying mechanisms of CD8+CD25+Treg in pathogenesis of malignant tumors, autoimmune diseases and other common diseases such as asthma, allergic diseases, type 2 diabetes, and pre-eclampsia. The changes of CD8+CD25+Treg in different diseases are inconsistent, cell counting increased in malignant diseases but decreased in autoimmune diseases. Further understanding of CD8+CD25+Treg would supporte a basis for the prevention, treatment and improving prognosis of these diseases.

Post-stroke hemiplegia usually has an adverse impact on motor ability and stability. Patients often develop shoulder subluxation and abnormal gait due to muscle weakness， bilateral limb muscle tension imbalance， sensory abnormalities and poor joint and posture control， etc. Shoulder orthosis is often used to prevent or treat shoulder subluxation in the early stage of stroke hemiplegia， but it is still controversial. To explore the role of shoulder orthosis beyond the prevention and treatment of shoulder subluxation， and to provide theoretical basis for the selection and wearing of shoulder orthosis，the mechanism underlying the role of shoulder orthosis in improving abnormal gait post-stroke hemiplegia was elaborated， and the effects of different types of shoulder orthosis on the rehabilitation of abnormal gait post-stroke were compared.

Abstract Background This overview summarizes the best available systematic review (SR) evidence on the health effects of Tai Chi. Methods Nine databases (PubMed, Cochrane Library, EMBASE, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Sino-Med, and Wanfang Database) were searched for SRs of controlled clinical trials of Tai Chi interventions published between Jan 2010 and Dec 2020 in any language. Effect estimates were extracted from the most recent, comprehensive, highest-quality SR for each population, condition, and outcome. SR quality was appraised with AMSTAR 2 and overall certainty of effect estimates with the GRADE method. Results Of the 210 included SRs, 193 only included randomized controlled trials, one only included non-randomized studies of interventions, and 16 included both. Common conditions were neurological (18.6%), falls/balance (14.7%), cardiovascular (14.7%), musculoskeletal (11.0%), cancer (7.1%), and diabetes mellitus (6.7%). Except for stroke, no evidence for disease prevention was found; however, multiple proxy-outcomes/risks factors were evaluated. One hundred and fourteen effect estimates were extracted from 37 SRs (2 high, 6 moderate, 18 low, and 11 critically low quality), representing 59,306 adults. Compared to active and/or inactive controls, 66 of the 114 effect estimates reported clinically important benefits from Tai Chi, 53 reported an equivalent or marginal benefit, and 6 an equivalent risk of adverse events. Eight of the 114 effect estimates (7.0%) were rated as high, 43 (37.7%) moderate, 36 (31.6%) low, and 27 (23.7%) very low certainty evidence due to concerns with risk of bias (92/114, 80.7%), imprecision (43/114, 37.7%), inconsistency (37/114, 32.5%), and publication bias (3/114, 2.6%). SR quality was often limited by the search strategies, language bias, inadequate consideration of clinical, methodological, and statistical heterogeneity, poor reporting standards, and/or no registered SR protocol. Conclusions The findings suggest Tai Chi has multidimensional effects, including physical, psychological and quality of life benefits for a wide range of conditions, as well as multimorbidity. Clinically important benefits were most consistently reported for Parkinson’s disease, falls risk, knee osteoarthritis, low back pain, cerebrovascular, and cardiovascular diseases including hypertension. For most conditions, higher-quality SRs with rigorous primary studies are required. Systematic review registration PROSPERO CRD42021225708.

The Tamm-Horsfall protein (THP), also known as uromodulin (UMOD), is a kidney-derived protein released bidirectionally in the blood and urine. Blood and urinary THP may be markers of early predictive diagnosis of acute kidney injury(AKI) and possibly as one of the indicators of AKI severity. At the same time, THP plays a role in protecting kidney function in AKI through inhibiting reactive oxygen species accumulation, anti-inflammatory response and regulating macrophages. So it is a potential target in the clinical treatment of AKI.

Artificial intelligence technology is the outcome of economic globalization. With the advent of the digital age, artificial intelligence plays an increasingly important role in various fields including the constantly updated and iterative healthcare and clinical service. Diabetes is a chronic non-communicable disease characterized by hyperglycemia. Many scholars are committed to researching diabetes prediction, intelligent diagnosis, early screening of complication and health management from an innovative perspective, so as to promote the health state of people. This paper mainly summarizes the application of artificial intelligence in diabetes research and clinical practice in recent years and puts forward future prospects for the intelligence and automation of diabetes diagnosis and treatment.

Abstract Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine in China. Various varieties of Codonopsis Radix have different tastes. To make the flavor of processed food stable, two kinds of electronic sensory devices, electronic nose and electronic tongue, were used to establish a discrimination model to identify the botanical origin of each sample. The optimal model built on the 88 batches of samples was selected from the models trained with all combination of two pretreatment methods and three classification methods. A comparison were performed on the models trained on the data collected by electronic nose and electronic tongue. The results showed that the model trained on the fused dataset outperformed the models trained separately on the electronic nose data and electronic tongue data. The two preprocessing approaches could improve the prediction performance of all classification methods. Classification and Regression Tree approach performed better than Partial Least Square Discriminant Analysis and Linear Discriminant Analysis in terms of accuracy. But Classification and Regression Tree tends to assign the samples of minority class to the majority class. Meanwhile, Partial Least Square Discriminant Analysis keeps a good balance between the identification requirements of all the two groups of samples. Taking all the results above, the model built using the Partial Least Square Discriminant Analysis method on the fused data after z-score was used to identify the botanical origin of Codonopsis Radix.