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Abstract Background With the advent of the smart phone era, managing blood glucose at home through apps will become more common for older individuals with diabetes. Adult children play important roles in glucose management of older parents. Few studies have explored how adult children really feel about engaging in the glucose management of their older parents with type 2 diabetes mellitus (T2DM) through mobile apps. This study provides insights into the role perceptions and experiences of adult children of older parents with T2DM participating in glucose management through mobile apps. Methods In this qualitative study, 16 adult children of older parents with T2DM, who had used mobile apps to manage blood glucose for 6 months, were recruited through purposive sampling. Semi-structured, in-depth, face-to-face interviews to explore their role perceptions and experiences in remotely managing their older parents’ blood glucose were conducted. The Consolidated Criteria for Reporting Qualitative Research (COREQ) were followed to ensure rigor in the study. The data collected were analyzed by applying Colaizzi’s seven-step qualitative analysis method. Results Six themes and eight sub-themes were identified in this study. Adult children’s perceived roles in glucose management of older parents with T2DM through mobile apps could be categorized into four themes: health decision-maker, remote supervisor, health educator and emotional supporter. The experiences of participation could be categorized into two themes: facilitators to participation and barriers to participation. Conclusion Some barriers existed for adult children of older parents with T2DM participating in glucose management through mobile apps; however, the findings of this study were generally positive. It was beneficial and feasible for adult children to co-manage the blood glucose of older parents. Co-managing blood glucose levels in older parents with T2DM can enhance both adherence rates and confidence in managing blood glucose effectively.

Diffusion Innovation theory aims to elaborate the law of diffusion and development of innovation things in social systems and is widely used in the study of diffusion phenomena of new technologies at home and abroad. As digital transformation reshapes global communication and learning styles, the recent advances in wearable and portable brain-computer interfaces (BCI) provide an opportunity for practical implementation in educational scenarios, have a broad application prospect. Here, we review the four ways BCI is currently applied in the field of education based on the functional classification of BCI. Next, specific factors of the innovation diffusion process of BCI in the education field are discussed within the framework of the Innovation Diffusion theory, and summaries the commercialized products of BCI in education under the four application modes, and the development route of BCI in education in the future. Based on the collected data, we believe that the current application of BCI systems in the education field is still in the initial stage of innovation diffusion, with slow diffusion. Finally, several strategies aiming to accelerate the application of BCI in the field of education are proposed and discussed, which we are hoping to have both theoretical and practical significance.

BackgroundFrailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States.MethodsThis study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot.ResultsThis study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24–1.54) and 1.69 (1.53–1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55–2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10–1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95–2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty.ConclusionThe results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Objectives: To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). Methods: This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. Results: A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. Conclusion: ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. Clinical trials registration: ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

The plants that comprise the vegetation of Chinese subtropics are diverse with respect to geographical distribution patterns. Understanding how the plants with different geographical distribution patterns that live together in this region differ in their ecological niches, would advance our knowledge of species coexistence mechanisms. Here, based on the data of woody angiosperm community composition in eight broad-leaved forest dynamics plots widely distributed in the Chinese subtropics, by adopting statistical methods such as phylogenetic linear model and analysis of variance (ANOVA), we examined the differences in life history traits, including leaf habit and growth form, as well as ecological behaviors (i.e., Ellenberg indicator values), between the plants of temperate distribution pattern genera and the plants of tropical distribution pattern genera. The results were as follows: (1) For the 265 study genera, distribution pattern genus showed a significant phylogenetic signal (i.e., Pagel's λ = 0.935, P< 0.001). (2) The temperate distribution pattern genera comprised a higher ratio of deciduous broad-leaved plants and trees than the tropical distribution pattern genera, and there were more evergreen broad-leaved plants and shrub in tropical distribution pattern. (3) The plants of temperate distribution pattern genera exist in environments with high light, low temperature and water compared with the plants of tropical distribution pattern genera, regardless of the effects of leaf habit and growth form were controlled or not. (4) For all the plants, or for each leaf habit or growth form group separately, the ratio of species richness of the temperate distribution pattern genera to the tropical distribution pattern genera in the forest was controlled by mean annual temperature (MAT). The findings imply that the plants of temperate and tropical distribution pattern genera differe in both their life history traits as well as their ecological behaviors, and the geographical turnover of plants of these two distribution patterns in the Chinese subtropical broad-leaved forests is largely controlled by MAT.

At the heart of the non-implantable electronic revolution lies ionogels, which are remarkably conductive, thermally stable, and even antimicrobial materials. Yet, their potential has been hindered by poor mechanical properties. Herein, a double network (DN) ionogel crafted from 1-Ethyl-3-methylimidazolium chloride ([Emim]Cl), acrylamide (AM), and polyvinyl alcohol (PVA) was constructed. Tensile strength, fracture elongation, and conductivity can be adjusted across a wide range, enabling researchers to fabricate the material to meet specific needs. With adjustable mechanical properties, such as tensile strength (0.06–5.30 MPa) and fracture elongation (363–1373%), this ionogel possesses both robustness and flexibility. This ionogel exhibits a bi-modal response to temperature and strain, making it an ideal candidate for strain sensor applications. It also functions as a flexible strain sensor that can detect physiological signals in real time, opening doors to personalized health monitoring and disease management. Moreover, these gels’ ability to decode the intricate movements of sign language paves the way for improved communication accessibility for the deaf and hard-of-hearing community. This DN ionogel lays the foundation for a future in which e-skins and wearable sensors will seamlessly integrate into our lives, revolutionizing healthcare, human–machine interaction, and beyond.

Abstract Background Exercise plays a major role in helping patients with type 2 diabetes mellitus and sarcopenia to increase muscle mass and muscle strength. However, little is known about perceptions of exercise and exercise instruction in these patients. This study aimed to explore the perceptions of exercise and exercise instruction from the patient’s perspective. Methods In a descriptive qualitative study, semi-structured face-to-face in-depth interviews were conducted with 16 patients with type 2 diabetes mellitus and sarcopenia at a tertiary hospital. The Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines were followed to ensure rigor in the study. The interviews were analysed using a thematic analysis method. Results Four themes and 13 sub-themes were identified in this study. The four themes were knowledge-attitudes-practices surrounding exercise, motivators and barriers regarding exercise, and attitudes towards professional exercise instruction. Conclusion This study provides a detailed understanding of the knowledge-attitudes-practices, motivators and barriers regarding exercise among patients with type 2 diabetes mellitus and sarcopenia, as well as attitudes related to exercise instruction. The current findings can guide healthcare professionals, patients’ families, and policymakers to motivate patients to be physically active through policy initiatives and other types of incentives and programmes, such as providing more health education and holistic support, increasing family and friends’ companionship and care, and providing suitable exercise conditions.

Background: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. Objective: In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. Methods: The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. Results: The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77–0.82), 0.85 (0.81–0.89), and 0.87 (0.83–0.91) at 30 days after the priming series, 0.86 (0.83–0.89), 0.81 (0.76–0.85), and 0.86 (0.80–0.93) at one year after the priming series, and 0.96 (0.94–0.99), 0.89 (0.86–0.93), and 0.98 (0.93–1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. Conclusion: A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study’s clinical trial registry number is NCT04224519.

In order to evaluate the effect of intercropping of the hyperaccumulator, Solanum nigrum L. and wheat on the absorption and accumulation of cadmium (Cd) in wheat. The experiment was conducted with three replicates, which conducted on four Cd concentrations (0, 20, 40, 60 μmol L−1) in the Hoagland solution and using two planting patterns [monoculture wheat (MW), intercropping wheat and Solanum nigrum L. (IW，IS)]. The results showed that the addition of Cd in the solutions reduced the total root length by 19.08–55.98%, total root area by 12.35–44.48%, and total root volume by 16.01–46.00% of wheat plants. Intercropping with Solanum nigrum L. significantly reduced Cd contents by 28.3–47.2% and Cd accumulations by 10.08–32.43% in the roots of wheat. Transmission electron microscope (TEM) revealed that the root-tip cells of the monoculture wheat treated with Cd exhibited swollen spheres of intracellular mitochondria, disorderly arranged inner ridges of mitochondria, some damaged mitochondrial membranes, and deformed nuclear membranes. Many dense electron particles in the form of Cd were deposited in the cell gap, and the cell nucleus became smaller or even disappeared. Under the same Cd concentrations, root-tip cells of intercropped wheat showed much less density of electron particles, starch granules, and the damage to the nucleus and nuclear membrane by Cd.These results indicated that intercropping with Solanum nigrum L. reduced the Cd toxicity to wheat roots and decreased Cd uptake and accumulation in both the shoots and roots of the wheat.

Abstract Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

Saponins from bitter melon (BMS) are well-known to have various biological activities, especially in the field of fat-lowering. However, many gaps remain in our knowledge of BMS-induced fat reduction and health benefits. Here, we aimed to investigate the precise mechanism of BMS in alleviating fat accumulation in C. elegans and HepG2 cell line. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by phosphatidylethanolamine (PE) increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS largely depended on daf-16/FoxO1 and hlh-30/TFEB mediated lipophagy to reduce fat deposition. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of autophagy-related proteins, such as the phosphorylated AMPK and LC3B. In conclusion, our results elucidated the underlying mechanism of bitter melon saponins interfering with lipid metabolism from the autophagy point of view, which provide new insights into a nutraceutical to mitigate obesity.

BackgroundRectal hyposensitivity (RH) is not uncommon in patients with functional defecation disorder (FDD). FDD patients with RH are usually unsatisfied with their treatment.AimsThe aim of this study was to find the significance of RH in patients with FDD and the related factors of RH.MethodsPatients with FDD first completed clinical questionnaires regarding constipation symptoms, mental state, and quality of life. Then anorectal physiologic tests (anorectal manometry and balloon expulsion test) were performed. Rectal sensory testing (assessing rectal response to balloon distension using anorectal manometry) was applied to obtain three sensory thresholds. Patients were separated into three groups (non-RH, borderline RH, and RH) based on the London Classification. The associations between RH and clinical symptoms, mental state, quality of life, and rectal/anal motility were investigated.ResultsOf 331 included patients with FDD, 87 patients (26.3%) had at least one abnormally elevated rectal sensory threshold and 50 patients (15.1%) were diagnosed with RH. Patients with RH were older and mostly men. Defecation symptoms were more severe (p = 0.013), and hard stool (p

Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic-ischemic injury and exploring the underlying mechanisms. Methods Primary cortical neurons were cultured and subjected to oxygen–glucose deprivation (OGD), and then treated with Scu administration. The growth status of neurons was observed by immunofluorescence staining of TUJ1 and TUNEL. Besides, the mRNA level of growth-associated protein 43 (GAP43) in OGD neurons with Scu treatment was detected by quantitative real-time polymerase chain reaction (qRT-PCR). To further verify the role of GAP43 in Scu treatment, GAP43 siRNA and knockout were applied in vitro and in vivo. Moreover, behavioral evaluations were performed to elucidate the function of GAP43 in the Scu-ameliorated long-term neurological impairments caused by HI insult. The underlying biological mechanism of Scu treatment was further elucidated via network pharmacological analysis. Finally, the interactive genes with GAP43 were identified by Gene MANIA and further validated by qRT-PCR. Results Our data demonstrated that Scu treatment increased the number of neurons and axon growth, and suppressed cell apoptosis in vitro. And the expression of GAP43 was downregulated after OGD, but reversed by Scu administration. Besides, GAP43 silencing aggravated the Scu-ameliorated neuronal death and axonal damage. Meanwhile, GAP43 knockout enlarged brain infarct area and deteriorated the cognitive and motor dysfunctions of HI rats. Further, network pharmacological analysis revealed the drug targets of Scu participated in such biological processes as neuronal death and regulation of neuronal death, and apoptosis-related pathways. GAP43 exhibited close relationship with PTN, JAK2 and STAT3, and GAP43 silencing upregulated the levels of PTN, JAK2 and STAT3. Conclusions Collectively, our findings revealed Scu treatment attenuated long-term neurological impairments after HI by suppressing neuronal death and enhancing neurite elongation through GAP43-dependent pathway. The crucial role of Scutellarin in neuroprotection provided a novel possible therapeutic agent for the treatment of neonatal HIE. Graphic abstract

Diabetic foot infections (DFIs) represent a frequent complication of diabetes and a major cause of amputations. This study aimed to evaluate the utility of 16S rRNA gene sequencing for the rapid microbiological diagnosis of DFIs and to consistently characterize the microbiome of chronic diabetic foot ulcers (DFUs) and intact skin. Wound samples were collected by ulcer swabbing and tissue biopsy, and paired swabs of intact skin were collected from 10 patients with DFIs (five were moderately infected, and the other five were severely infected). Samples were analyzed by conventional culture and using Personal Genome Machine (PGM) 16S rRNA sequencing technology. The results showed that PGM technology detected significantly more bacterial genera (66.1 vs. 1.5 per wound sample, p 0.05). The bacterial community on intact skin was significantly more diverse than that in DFUs (Chao1 value, p

Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) represents as a major cause of neonatal morbidity and mortality. However, the underlying molecular mechanisms in brain damage are still not fully elucidated. This study was conducted to determine the specific potential molecular mechanism in the hypoxic-ischemic induced cerebral injury. Methods Here, hypoxic-ischemic (HI) animal models were established and primary cortical neurons were subjected to oxygen–glucose deprivation (OGD) to mimic HIE model in vivo and in vitro. The HI-induced neurological injury was evaluated by Zea-longa scores, Triphenyte-trazoliumchloride (TTC) staining the Terminal Deoxynucleotidyl Transferased Utp Nick End Labeling (TUNEL) and immunofluorescent staining. Then the expression of Cytochrome c oxidase subunit 5a (COX5A) was determined by immunohistochemistry, western blotting (WB) and quantitative real time Polymerase Chain Reaction (qRT-PCR) techniques. Moreover, HSV-mediated COX5A over-expression virus was transducted into OGD neurons to explore the role of COX5A in vitro, and the underlying mechanism was predicted by GeneMANIA, then verified by WB and qRT-PCR. Results HI induced a severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats, in corresponding to the decrease on the expression of COX5A in both sides of the brain. What’s more, COX5A over-expression significantly promoted the neuronal survival, reduced the apoptosis rate, and markedly increased the neurites length after OGD. Moreover, Triosephosephate isomerase (TPI) was predicted as physical interactions with COX5A, and COX5A over-expression largely increased the expressional level of TPI. Conclusions The present findings suggest that COX5A plays an important role in promoting neurological recovery after HI, and this process is related to TPI up-regulation.

Abstract Background The limited neuronal differentiation of the endogenous or grafted neural stem cells (NSCs) after brain injury hampers the clinic usage of NSCs. Panax notoginseng saponins (PNS) were extensively used for their clinical value, such as in controlling blood pressure, blood glucose, and inhibiting neuronal apoptosis and enhancing neuronal protection, but whether or not it exerts an effect in promoting neuronal differentiation of the endogenous NSCs is completely unclear and the potential underlying mechanism requires further exploration. Methods Firstly, we determined whether PNS could successfully induce NSCs to differentiate to neurons under the serum condition. Mass spectrometry and quantitative polymerase chain reaction (Q-PCR) were then performed to screen the differentially expressed proteins (genes) between the PNS + serum and serum control group, upon which dihydropyrimidinase-like 2 (DPYSL2), a possible candidate, was then selected for the subsequent research. To further investigate the actual role of DPYSL2 in the NSC differentiation, DPYSL2-expressing lentivirus was employed to obtain DPYSL2 overexpression in NSCs. DPYSL2-knockout rats were constructed to study its effects on hippocampal neural stem cells. Immunofluorescent staining was performed to identify the differentiation direction of NSCs after 7 days from DPYSL2 transfection, as well as those from DPYSL2-knockout rats. Results Seven differentially expressed protein spots were detected by PD Quest, and DPYSL2 was found as one of the key factors of NSC differentiation in a PNS-treated condition. The results of immunostaining further showed that mainly Tuj1 and GFAP-positive cells increased in the DPYSL2-overexpressed group, while both were depressed in the hippocampal NSCs in the DPYSL2-knockout rat. Conclusions The present study revealed that the differentiation direction of NSCs could be enhanced through PNS administration, and the DPYSL2 is a key regulator in promoting NSC differentiation. These results not only emphasized the effect of PNS but also indicated DPYSL2 could be a novel target to enhance the NSC differentiation in future clinical trials.

Abstract Background Colorectal cancer, one of the most common digestive tumors with high mortality and morbidity worldwide, currently lacks effective therapies available to improve the prognosis. This study was aimed to investigate the potency of Scutellarin against colorectal cancers, and explore the related mechanism via genomic and proteomic analysis. Methods Cell counting kit-8 assay was employed to detect the viability of HCT-116 and RKO cell lines treated with Scutellarin. The apoptosis of HCT-116 and RKO cells after Scutellarin administration was determined by TUNEL staining and Caspase 3/7 activity. Cell cycle was detected by flow cytometry analysis. The wound healing and transwell invasion test detected the role of Scutellarin in migration and invasion of HCT-116 and RKO cells. Meanwhile, the energy metabolism and growth of tumor tissues in vivo at day 28 were observed by PET-CT after Scutellarin administration with 50 mg/kg, 100 mg/kg and 300 mg/kg into 4-week-old nude mice. Blood routine and liver functions were also detected to evaluate the side effect of Scutellarin. Furthermore, the disease and function classifications which the differentially expressed genes and proteins involved after Scutellarin treatment were determined by genomic and proteomic analysis respectively. Results The Scutellarin inhibited the migration and increased apoptosis of HCT-116 and RKO cell lines. Besides, Scutellarin treatment substantially decreased the growth and volume of colorectal tumors in nude mice without side effects on the blood routine and liver function. The differentially expressed genes in RKO cells after Scutellarin administration were mainly enriched in cell death and survival, organismal injury and abnormalities, and cancer. In addition, forty-seven upregulated and twenty-nine downregulated proteins were identified. Functional clustering analysis exhibited enriched biological processes, cellular components, molecular functions and related pathways of these proteins in cellular metabolic. Then protein–protein interactions analysis showed the regulatory relationship among these differentially expressed proteins. Conclusions Taken together, the present findings revealed that Scutellarin exerted significant antitumor effect with no side effects in the blood and liver by regulating various important molecules in tumor proliferation, apoptosis and metastasis.

Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease, often resulting in long-term neurodevelopmental disorders among surviving children. However, whether these neurodevelopmental issues can be passed to offspring remains unclear. The right common carotid artery of 7-day-old parental-generation rats was subjected to permanent ligation using a vessel electrocoagulator. Neonatal hypoxic-ischemic rat models were established by subjecting the rats to 8% O2–92% N2 for 2 hours. The results showed that 24 hours after hypoxia and ischemia, pathological damage, cerebral atrophy, liquefaction, and impairment were found, and Zea-Longa scores were significantly increased. The parental-generation rats were propagated at 3 months old, and offspring were obtained. No changes in the overall brain structures of these offspring rats were identified by magnetic resonance imaging. However, the escape latency was longer and the number of platform crossings was reduced among these offspring compared with normal rats. These results indicated that the offspring of hypoxic-ischemic encephalopathy model rats displayed cognitive impairments in learning and memory. This study was approved by the Animal Care & Welfare Committee of Kunming Medical University, China in 2018 (approval No. kmmu2019072).

Abstract Aims Understanding the joint effects of plant development and environment on shifts of intraspecific leaf traits will advance the understandings of the causes of intraspecific trait variation. We address this question by focusing on a widespread species Clausena dunniana in a subtropical broad‐leaved forest. Methods We sampled 262 individuals of C. dunniana at two major topographic habitat types, the slope and hilltop, within the karst forests in Maolan Nature Reserve in southwestern China. We measured individual plant level leaf traits (i.e., specific leaf area (SLA), leaf area, leaf dry‐matter content (LDMC), and leaf thickness) that are associated with plant resource‐use strategies. We adopted a linear mixed‐effects model in which the plant size (i.e., the first principal component of plant basal diameter and plant height) and environmental factors (i.e., topographic habitat, canopy height, and rock‐bareness) were used as independent variables, to estimate their influences on the shifts of leaf traits. Key Results We found that (1) plant size and the environmental factors independently drove the intraspecific leaf trait shifts of C. dunniana, of which plant size explained less variances than environmental factors. (2) With increasing plant size, C. dunniana individuals had increasingly smaller SLA but larger sized leaves. (3) The most influential environmental factor was topographic habitat; it drove the shifts of all the four traits examined. Clausena dunniana individuals on hilltops had leaf traits representing more conservative resource‐use strategies (e.g., smaller SLA, higher LDMC) than individuals on slopes. On top of that, local‐scale environmental factors further modified leaf trait shifts. Conclusions Plant size and environment independently shaped the variations in intraspecific leaf traits of C. dunniana in the subtropical karst forest of Maolan. Compared with plant size, the environment played a more critical role in shaping intraspecific leaf trait variations, and potentially also the underlying individual‐level plant resource‐use strategies.

Background: The London Classification for anorectal physiological dysfunction specifically proposes rectoanal areflexia (RA), which means the absence of a rectoanal inhibitory reflex (RAIR) based on a manometric diagnosis. Although RA is not observed in healthy people, it can be found in adult patients with functional constipation (FC). This study describes the clinical manifestations of adult patients with FC and RA and their response to biofeedback therapy (BFT). Methods: This retrospective study reviewed the reports of high-resolution anorectal manometry (HR-ARM) and the efficacy of BFT in adult patients with FC. In addition, the Constipation Scoring System (CSS) scale, Patient Assessment of Constipation Symptoms (PAC-SYM) scale, Patient Assessment of Constipation Quality of Life (PAC-QOL) scale, Zung’s Self-Rating Anxiety Scale (SAS), Zung’s Self-Rating Depression Scale (SDS), balloon expulsion test (BET), and the use of laxatives were assessed. Results: A total of 257 adult patients diagnosed with FC were divided into the RA group (n = 89) and the RAIR group (n = 168). In the RA and RAIR groups, 60 (67.4%) and 117 (69.6%) patients, respectively, had dyssynergic defecation (DD) during simulated defecation. Type II pattern of dyssynergia was most frequently observed in both groups. Compared with the RA group, the RAIR group showed a higher CSS score, physical discomfort score, and prevalence of inadequate relaxation of the anal sphincter (p < 0.001, p = 0.036, and p = 0.017, respectively). The anxiety and depression scores were not different between the two groups. The proportion of patients using volumetric and stimulant laxatives and their combination was significantly higher in FC patients with RA, whereas the efficacy of BFT was significantly lower (p = 0.005, p < 0.001, p = 0.045, and p = 0.010, respectively). Conclusion: Adult FC patients with RA may suffer more severe constipation and have a lower efficacy of BFT compared with those with RAIR.

Abstract Cisplatin (CP), an anticancer drug, often causes kidney damage. However, the mechanism of CP‐induced acute kidney injury (AKI) is not completely understood. AKI was induced by intravenous injection (i.v.) of cisplatin at doses of 5, 8, and 10 mg/kg. Anemoside B4 (B4) (20 mg/kg, i.m.) and dexamethasone (DXM) (0.5 mg/kg, i.v.) were used for AKI treatment. Biochemical indicators were assessed using an automatic biochemical analyzer, protein expression was analyzed by western blotting, and morphological changes in the kidney were examined by PAS staining. The serum creatinine (Cre) and blood urea nitrogen (BUN) levels did not change significantly in the first 2 days but abruptly increased on the third day after CP injection. The serum albumin (ALB) and total protein (TP) levels decreased in both a time‐ and dose‐dependent manner. The urine protein level increased, the clearing rate of Cre decreased distinctly, and morphologic changes appeared in a dose‐dependent manner. The protein expression of p53/caspase‐3, NLRP3, IL‐6, and TNF‐α was obviously upregulated on day 3; concurrently, nephrin and podocin were downregulated. The expression of LC3II and p62 was upregulated significantly as the CP dose increased. B4 and DXM obviously decreased the BUN and Cre levels after 3 or 5 days of treatment. AKI appeared distinctly in a time‐dependent manner at 2 to 5 days after the administration of 5 mg/kg CP and in a dose‐dependent manner upon the administration of 5, 8, and 10 mg/kg CP. The third day was a significant time point for renal deterioration, and treatment with B4 and DXM within the first 3 days provided significant protection against AKI.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). Our previous study suggested that the expression of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is closely related to DGP. However, the role of MALAT1 in DGP pathogenesis remains unclear. Here, we aim to characterize the role of MALAT1 in DGP. First, we analyzed the lncRNA expression profiles through lncRNA sequencing. Next, we detected MALAT1 expression in the stomach tissues of DGP model mice and diabetic patients. Then, we investigated the role and mechanisms of MALAT1 in the proliferation, migration, phenotypic switch, and carbachol-induced intracellular Ca2+ changes in human gastric smooth muscle cells (HGSMCs) under high glucose (HG) conditions, using short hairpin RNA technology, RNA immunoprecipitation, and dual-luciferase reporter assays. We show that MALAT1 expression was upregulated in the gastric tissues of DGP model mice, the adjacent healthy tissues collected from diabetic gastric cancer patients with DGP symptoms, and in HGSMCs cultured under HG conditions. Functionally, MALAT1 knockdown in vitro impacted the viability, proliferation, migration and promoted the phenotypic switch of HGSMCs under HG conditions. Additionally, we show that MALAT1 sponged miR-449a, regulating Delta-like ligand 1 (DLL1) expression in HGSMCs; any disturbance of the MALAT1/miR-449a/DLL1 pathway affects the proliferation, migration, phenotypic switch, and carbachol-induced Ca2+ transient signals in HGSMCs under HG conditions. Collectively, our data highlight a novel regulatory signaling pathway, the MALAT1/miR-449a/DLL1 axis, in the context of DGP.

Aurora-A kinase is frequently over-expressed in tumours. Here, the authors show that it modulates the activity of lactate dehydrogenase B, resulting in enhanced glycolysis, bio-synthesis and tumour growth.

Objectives: Gastro-esophageal reflux disease (GERD) is a common disease in gastroenterology outpatients. However, some patients with typical reflux symptoms does not satisfy diagnostic criteria. This study was to explore the value of adjunctive evidence from multichannel intraluminal impedance-pH (MII-pH) monitoring and esophageal high-resolution manometry (HRM) in inconclusive GERD patients with acid exposure time (AET) 4–6%. Methods: Endoscopy, MII-pH monitoring and esophageal HRM were retrospectively analyzed from consecutive patients with typical reflux symptoms in a tertiary hospital from 2013 to 2019. Patients were categorized as conclusive or inconclusive GERD according to AET. Adjunctive evidence for GERD diagnosis from Lyon Consensus were collected and analyzed. Results: Among 147 patients with typical reflux symptoms, conclusive GERD was found in only 31.97% of patients ( N = 47). The remaining 100 patients (68.03%) were inconclusive GERD, of whom 28% ( N = 28) had AET 4–6%. These patients suffered similar reflux burden and impaired esophageal movement. Inconclusive GERD patients with AET 4–6% had lots of positive adjunctive evidence from HRM and MII-pH monitoring. In receiver operating characteristic analysis, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWI) had an area under the curve (AUC) of 0.839 (CI: 0.765–0.913, p

Background: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) plays an important role in poliomyelitis eradication in developing countries. As part of the phase III clinical development program, this study aimed to evaluate the safety, immunogenicity and lot-to-lot consistency of the sIPV in 2-month-old infants. Method: We conducted a phase III, randomized, double-blind, positive-controlled trial in which 1300 healthy infants were randomly assigned to four groups in a 1:1:1:1 ratio to receive one of the three lots of the sIPV or the control IPV at 2, 3 and 4 months of age. Serum samples were collected before the first dose and 30 days after the third dose of vaccination to assess the immunogenicity. Solicited local and systemic reactions were recorded within 7 days and unsolicited adverse events within 30 days after each vaccination. Results: Of the 1300 randomized infants, 1190 infants completed the study and were included in the per-protocol population. The seroconversion rates in the three lots of the sIPV were 95.67%, 97.03% and 95.59%, respectively, for type 1; 94.33%, 93.73% and 92.88%, respectively, for type 2; and 98.67%, 99.67% and 99.32%, respectively, for type 3. The ratios of GMTs for poliovirus types 1, 2 and 3 of each pair of lots were all between 0.67 and 1.50, therefore meeting the predefined immunological equivalence criteria. For the seroconversion rate of poliovirus types 1, 2 and 3, the pooled sIPV group was non-inferior to the IPV group. The incidence of solicited and unsolicited adverse reactions (ARs) was similar in the pooled sIPV lots and the IPV group, and most of them were mild to moderate in severity. Non-vaccine-related serious adverse events (SAEs) were reported. Conclusions: Three consecutive lots of sIPV demonstrated robust and consistent immunogenicity. The safety and tolerability of the sIPV was acceptable and similar to that of the IPV.

Cerebral ischemia (CI) is a severe brain injury resulting in a variety of motor impairments combined with secondary injury in remote organs, especially the lung. This condition occurs due to insufficient blood supply to the brain during infancy. However, it has a molecular linkage that needs to be thoroughly covered. Here, we report on the role of vascular endothelial growth factor C (VEGFC) in lung injury induced by CI. The middle cerebral artery occlusion (MCAO) was depended to establish the animal model of CI. Rats were used and brain ischemia was confirmed through TTC staining. Serum was used for protein chip analysis to study the proteomic interaction. Immunohistochemistry analyses were used to quantify and locate the VEGFC in the lung and brain. The role of VEGFC was detected by siVEGFC technology in SY5Y, HUCEV, and A549 cell lines, under normal and oxygen glucose deprivation (OGD) conditions in vitro. As a result, the TTC staining demonstrated that the model of brain ischemia was successfully established, and MPO experiments reported that lung damage was induced in MCAO rats. VEGFC levels were up-regulated in serum. On the other hand, immunohistochemistry showed that VEGFC increased significantly in the cytoplasm of neurons, the endothelium of small trachea and the lung cells of CI animals. On a functional level, siVEGFC effectively inhibited the proliferation of SY5Y cells and decreased the viability of HUVEC cells in normal cell lines. But under OGD conditions, siVEGFC decreased the growth of HUVEC and increased the viability of A549 cells, while no effect was noticed on SYSY cells. Therefore, we confirmed the different role of VEGFC played in neurons and lung cells in cerebral ischemia-reperfusion injury. These findings may contribute to the understanding the molecular linkage of brain ischemia and lung injury, which therefore provides a new idea for the therapeutic approach to cerebral ischemia-reperfusion.

The traditional concept of "tonic food" and demand for traditional Chinese medicine make pangolins the largest population of illegally smuggled mammals in the world. Illegal hunting and trade are not only responsible for the sharp decline in pangolin populations but also provide conditions for pathogenic transmission. In 2021, we rescued 21 confiscated unhealthy Malayan pangolins, none of which survived. This study aimed to investigate the reasons for their unexpected deaths and the potential pathogens that may be transmitted during smuggling. Physical examination found that more than 80% pangolins were parasitized with A. javanense ticks. Autopsy and pathological staining analysis revealed multiple organ damage in the deceased pangolins. Pathogens nucleic acid detection of 33 tick samples showed that the positive rate of Rickettsia spp., Anaplasma spp., Ehrlichia spp. Babesia spp., and Colpodella spp. were 90.91%, 6.06%, 6.06%, 15.15% and 18.18%, respectively. Furthermore, pangolin samples were positive for Rickettsia spp. (42.86%, 9/21), Ehrlichia sp. (4.76%, 1/21), and Babesia sp. (4.76%, 1/21). This study confirmed that spotted fever triggered by Rickettsia spp. from A. javanense might accelerate the most death of confiscated pangolins, while Ehrlichia sp., and Babesia sp. infection potentially accelerating a few deaths. Of note, A. javanense ticks carrying Colpodella spp. were detected for the first time in Malayan pangolins. However, whether Colpodella spp. are pathogenic to pangolins is unknown. Further research on the diagnosis, treatment, surveillance, and elimination of ticks and tick-borne diseases in humans, livestock, and wildlife should provide insight into wildlife conservation and zoonotic disease prevention.

Objective. To compare the efficacy of swabbing versus tissue biopsy for microbiological diagnosis of diabetic foot infection. Methods. This was a prospective trial. Fifty-six patients with diabetic foot infection were divided into the following 3 groups according to the PEDIS grading system: grade 2 (n=10), grade 3 (n=29), and grade 4 (n=17). Two specimens were collected from each wound for microbial culturing after debridement, including a superficial swab and a deep tissue punch biopsy specimen. Results. Swab culturing identified all of the microorganisms isolated from the corresponding deep tissue specimens in 9/10 of grade 2 wounds (90.0%), and this proportion decreased to 12/29 (41.4%) and 7/17 (41.2%) for grades 3 and 4 wounds, respectively (p=0.02). Moreover, the sensitivity for identifying Gram-negative bacteria, such as E. coli and Citrobacter, by swabbing was low (33.3%). In addition, some Gram-negative bacteria, such as Serratia and Ralstonia pickettii, were isolated from deep tissues but not from swabs. Conclusions. Swab culturing may be reliable for identification of pathogens in diabetic foot wounds classified as grade 2. However, it is advisable to culture deep tissue specimens for wounds of grade ≥3 because swab culturing is associated with a high risk of missing pathogens, especially Gram-negative bacteria.

Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, the leading cause of viral-induced encephalitis. Several host molecules have been identified as the JEV attachment factor; however, the molecules involved in JEV entry remain poorly understood. In the present study, we demonstrate that TIM-1 is important for efficient infection by JEV. Firstly, three TIM-1 variants (V1, V2, and V3) were cloned from A549 cells, and we revealed that only ectopically TIM-1 V2 expression in 293T cells significantly promotes JEV attachment, entry and infection. Point mutation of phosphatidylserine (Ptdser) binding pocket in the TIM-1 IgV domain dampened JEV entry, indicating that TIM-1-mediated JEV infection is Ptdser-dependent. Furthermore, we found the cytoplasmic domain of TIM-1 is also required for enhancing JEV entry. Additionally, knock down of TIM-1 expression in A549 cells impaired JEV entry and infection, but not attachment, suggesting that additional factors exist in A549 cells that allow the virus to bind. In conclusion, our findings demonstrate that TIM-1 promotes JEV infection as an entry cofactor, and the polymorphism of TIM-1 is associated with JEV susceptibility to host cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Despite the substantial role that chickens have played in human societies across the world, both the geographic and temporal origins of their domestication remain controversial. To address this issue, we analyzed 863 genomes from a worldwide sampling of chickens and representatives of all four species of wild jungle fowl and each of the five subspecies of red jungle fowl (RJF). Our study suggests that domestic chickens were initially derived from the RJF subspecies Gallus gallus spadiceus whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. Following their domestication, chickens were translocated across Southeast and South Asia where they interbred locally with both RJF subspecies and other jungle fowl species. In addition, our results show that the White Leghorn chicken breed possesses a mosaic of divergent ancestries inherited from other subspecies of RJF. Despite the strong episodic gene flow from geographically divergent lineages of jungle fowls, our analyses show that domestic chickens undergo genetic adaptations that underlie their unique behavioral, morphological and reproductive traits. Our study provides novel insights into the evolutionary history of domestic chickens and a valuable resource to facilitate ongoing genetic and functional investigations of the world's most numerous domestic animal.

The traditional concept of "tonic food" and demand for traditional Chinese medicine make pangolins the largest population of illegally smuggled mammals in the world. Illegal hunting and trade are not only responsible for the sharp decline in pangolin populations but also provide conditions for pathogenic transmission. In 2021, we rescued 21 confiscated unhealthy Malayan pangolins, none of which survived. This study aimed to investigate the reasons for their unexpected deaths and the potential pathogens that may be transmitted during smuggling. Physical examination found that more than 80% pangolins were parasitized with A. javanense ticks. Autopsy and pathological staining analysis revealed multiple organ damage in the deceased pangolins. Pathogens nucleic acid detection of 33 tick samples showed that the positive rate of Rickettsia spp., Anaplasma spp., Ehrlichia spp. Babesia spp., and Colpodella spp. were 90.91%, 6.06%, 6.06%, 15.15% and 18.18%, respectively. Furthermore, pangolin samples were positive for Rickettsia spp. (42.86%, 9/21), Ehrlichia sp. (4.76%, 1/21), and Babesia sp. (4.76%, 1/21). This study confirmed that spotted fever triggered by Rickettsia spp. from A. javanense might accelerate the most death of confiscated pangolins, while Ehrlichia sp., and Babesia sp. infection potentially accelerating a few deaths. Of note, A. javanense ticks carrying Colpodella spp. were detected for the first time in Malayan pangolins. However, whether Colpodella spp. are pathogenic to pangolins is unknown. Further research on the diagnosis, treatment, surveillance, and elimination of ticks and tick-borne diseases in humans, livestock, and wildlife should provide insight into wildlife conservation and zoonotic disease prevention. Author summary: As a globally distributed obligate bloodthirsty ectoparasite, ticks are the vector second only to mosquitoes, capable of transmitting a variety of pathogenic viruses, bacteria, and protozoa to humans, livestock, and wildlife. Illegal poaching and smuggling pose a serious threat to the survival of pangolins and are also a potential route for the spread of tick-borne diseases. The present study was conducted to investigate the reasons for the unexpected death of Malayan pangolins confiscated in 2021, as well as to explore the potential pathogens that may be transmitted during smuggling. Based on the clinical symptoms, autopsy, and molecular detection results, we speculate that the primary cause was the spotted fever triggered by Rickettsia spp. from A. javanense, which accelerated the death of smuggled pangolins. Ehrlichia sp. or Babesia sp. infection might be associated with the death of a few pangolins. Moreover, A. javanense carrying Colpodella spp. were detected for the first time in Malayan pangolins, and whether Colpodella spp. are pathogenic to pangolins awaits further study. The findings suggest that more attention should be paid to the diagnosis and treatment of tick-borne diseases in the rescue operation of pangolins and other wildlife. [ABSTRACT FROM AUTHOR]