Search

Abstract Background As a novel and time-efficient exercise form, high-intensity interval training (HIIT) has shown great potential in improving health-related physical fitness among diverse populations. However, empirical evidence on its efficacy among the elderly has not been well summarized. This systematic review and meta-analysis aimed to determine the effect of HIIT interventions on the parameters related to physical fitness and health of older adults, including resting heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiorespiratory fitness (CRF), body mass index (BMI), body fat percent (BF%), waist circumference (WC), muscular endurance (ME), muscular strength (MS), muscular power (MP), balance and flexibility, compared to non-exercise and other-exercise (e.g., moderate-intensity continuous training, resistance training) conditions. Methods Literature published from January 2000 to May 2023 was collected through extensive searches across eight databases and relevant review papers. Randomized controlled trials (RCTs) featuring a minimum 2-week exercise intervention for older adults (≥ 60 years) were included. The pooled effect size of Hedges’g was estimated using random-effects models in R. Meta-regression was performed for both categorical (health status, duration of training programme, and frequency) and continuous moderators (mean age, male rate, and attrition rate). Results Forty-four eligible RCTs with 1863 participants (52.1% female; 60.5–81.2 years) were included in the quantitative analysis. Compared to non-exercise condition, HIIT significantly improved resting HR (g = -0.36, 95%CI = [-0.67, -0.05], P = 0.032), SBP (g = -0.29, 95%CI = [-0.54, -0.03], P = 0.008), CRF (g = 0.77, 95%CI = [0.51, 1.04], P 0.05). Meta-regression indicated that mean age moderated the HIIT effect on resting HR (b = -0.02, P = 0.014; HIIT vs. other-exercise condition) and SBP (b = 0.03, P = 0.048; HIIT vs. non-exercise), and attrition rate moderated the effect on CRF (b = 0.03, P = 0.007; HIIT vs. non-exercise). Conclusion This study supports the efficacy of HIIT in improving resting HR, SBP, CRF, BF%, MS, ME and balance among older adults. More empirical evidence is needed to determine the efficacy of HIIT for MP and flexibility in this population. Trial Registration PROSPERO CRD42022316246.

Tendinopathy leads to low-grade tissue inflammation and chronic damage, which progresses due to pathological imbalance in angiogenesis. Reducing early pathological vascularization may be a new approach in helping to regenerate tendon tissue. Conventional stem cell therapy and tissue engineering scaffolds have not been highly effective at treating tendinopathy. In this study, tissue engineered stem cells (TSCs) generated using human umbilical cord mesenchymal stem cells (hUC-MSCs) were combined with microcarrier scaffolds to limit excessive vascularization in tendinopathy. By preventing VEGF receptor activation through their paracrine function, TSCs reduced in vitro angiogenesis and the proliferation of vascular endothelial cells. TSCs also decreased the inflammatory expression of tenocytes while promoting their anabolic and tenogenic characteristics. Furthermore, local injection of TSCs into rats with collagenase-induced tendinopathy substantially reduced early inflammation and vascularization. Mechanistically, transcriptome sequencing revealed that TSCs could reduce the progression of pathological angiogenesis in tendon tissue, attributed to Rap1-mediated vascular inhibition. TSCs may serve as a novel and practical approach for suppressing tendon vascularization, and provide a promising therapeutic agent for early-stage clinical tendinopathy.

Abstract Background The anatomic structure of the anterior chamber (AC) helps to explain differences in refractive status in school-aged children and is closely associated with primary angle closure (PAC). The aim of this study was to quantify and analyze the anterior chamber and angle (ACA) characteristics in Chinese children with different refractive status by swept-source optical coherence tomography (SS-OCT). Methods In a cross-sectional observational study, 383 children from two primary schools in Shandong Province, China, underwent a complete ophthalmic examination. First, the anterior chamber depth (ACD), anterior chamber width (ACW), angle-opening distance (AOD), and trabecular-iris space area (TISA) were evaluated automatically using a CASIA2 imaging device. AOD and TISA were measured at 500, 750 μm nasal (N1 and N2, respectively), and temporal (T1 and T2, respectively) to the scleral spur (SS). Cycloplegic refraction and axial length (AL) were then measured. According to spherical equivalent refraction (SER), the children were assigned to hyperopic (SER > 0.50D), emmetropic (-0.50D

Abstract As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V. However, pretreatment with 5 mM NAC (ROS inhibitor) and 2 µM Rotenone (mitochondrial ETC inhibitor) reversed the autophagy induced by AA. In summary, AA modulates autophagy in SCs during HS by disrupting mitochondrial ETC function, inferring that the release of AA is a switch-like response, and providing insight into the underlying mechanism of high temperatures causing male infertility.

Abstract Background Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow. Methods We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case–control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES). Results Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES. Conclusions Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.

Quantum dot-based up-conversion photodetector, in which an infrared photodiode (PD) and a quantum dot light-emitting diode (QLED) are back-to-back connected, is a promising candidate for low-cost infrared imaging. However, the huge efficiency losses caused by integrating the PD and QLED together hasn’t been studied sufficiently. This work revealed at least three origins for the efficiency losses. First, the PD unit and QLED unit usually didn’t work under optimal conditions at the same time. Second, the potential barriers and traps at the interconnection between PD and QLED units induced unfavorable carrier recombination. Third, much emitted visible light was lost due to the strong visible absorption in the PD unit. Based on the understandings on the loss mechanisms, the infrared up-conversion photodetectors were optimized and achieved a breakthrough photon-to-photon conversion efficiency of 6.9%. This study provided valuable guidance on how to optimize the way of integration for up-conversion photodetectors.

Abstract Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Abstract Whether mice can be used as a foot-and-mouth disease (FMD) model has been debated for a long time. However, the major histocompatibility complex between pigs and mice is very different. In this study, the protective effects of FMD vaccines in different animal models were analyzed by a meta-analysis. The databases PubMed, China Knowledge Infrastructure, EMBASE, and Baidu Academic were searched. For this purpose, we evaluated evidence from 14 studies that included 869 animals with FMD vaccines. A random effects model was used to combine effects using Review Manager 5.4 software. A forest plot showed that the protective effects in pigs were statistically non-significant from those in mice [MH = 0.56, 90% CI (0.20, 1.53), P = 0.26]. The protective effects in pigs were also statistically non-significant from those in guinea pigs [MH = 0.67, 95% CI (0.37, 1.21), P = 0.18] and suckling mice [MH = 1.70, 95% CI (0.10, 28.08), P = 0.71]. Non-inferiority test could provide a hypothesis that the models (mice, suckling mice and guinea pigs) could replace pigs as FMDV vaccine models to test the protective effect of the vaccine. Strict standard procedures should be established to promote the assumption that mice and guinea pigs should replace pigs in vaccine evaluation.

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder (MDD). Vitamin D-binding protein (VDBP) is altered in plasma and postmortem dorsolateral prefrontal cortex (DLPFC) tissues of MDD patients. Thereby, the role of VDBP as a potential biomarker of MDD diagnosis was further assessed. Total extracellular vesicles (EVs) and brain cell-derived EVs (BCDEVs) were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls (HCs) in discovery (20 MDD patients and 20 HCs) and validation cohorts (88 MDD patients and 38 HCs). VDBP level in the cerebrospinal fluid (CSF) from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide (LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles (MDEVs). VDBP was significantly decreased in MDD plasma MDEVs compared to HCs, and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs. VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice. A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques. VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice. The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

Abstract Background Hip fractures are a major public health concern among middle-aged and older adults. It is important to understand the associated risk factors to inform health policies and develop better prevention strategies. Musculoskeletal pain is a possible implicating factor, being associated with physical inactivity and risk of falls. However, the association between musculoskeletal pain and hip fractures has not been clearly investigated. Methods A nationally representative sample of the Chinese population was obtained from the China Health and Retirement Longitudinal Study (CHARLS). The study collected patient information on their demographic characteristics, socioeconomic status, other health-related behavior, and history of musculoskeletal pain and hip fractures. Univariate and multivariate analyses were conducted to investigate the factors influencing the risk of hip fracture, including factors related to the individual and to musculoskeletal pain. P for trend test was performed to assess the trend of each continuous variable. The robustness and bias were assessed using the bootstrap method. Restricted cubic spline regression was utilized to identify linear or non-linear relationships. Results Among the 18,813 respondents, a total of 215 individuals reported that they have experienced a hip fracture. An increased risk of hip fracture was associated with the presence of waist pain and leg pain (P

Abstract Background Uniparental disomy (UPD) is a rare genetic condition leading to potential disease risks. Maternal UPD of chromosome 6 upd(6)mat is exceptionally rare, with limited cases reported. This study reported two new cases of upd(6)mat and reviewed the literature of previous cases. Case presentation Both cases exhibited intrauterine growth restriction (IUGR), and genetic analysis confirmed upd(6)mat in each case. The literature review identified a total of 19 cases. IUGR and preterm labor were the most common two symptoms observed, and additional anomalies and genetic variations were also reported in some cases. Conclusion upd(6)mat is potentially associatied with IUGR, but the precise genotype–phenotype relationship remains unclear. The cases with upd(6)mat may present clinical features due to imprinting disorders.

BackgroundTo understand the impact of individual preferences for specific dietary items on OA, and to help inform the development of effective and targeted OA prevention and management strategies, we performed a Mendelian randomization analysis between dietary preferences and osteoarthritis.MethodsThis study utilized genetic data from the UK Biobank to investigate the association between OA and 21 different common dietary items. Instrumental variables representing European populations were carefully selected based on their genetic significance and linkage disequilibrium. In cases where a dietary item had few relevant genetic markers, a more lenient selection threshold was applied. To prevent bias, the analysis excluded single nucleotide polymorphisms (SNPs) associated with factors such as body mass index (BMI) and cholesterol. Using inverse-variance weighting (IVW) and Mendelian randomization, significant associations were detected between certain dietary items and OA.ResultsUsing Mendelian randomization to examine the relationship between 21 different dietary items and OA, significant associations were found for coffee, peas, watercress, and cheese, where the first two had a promoting effect and the last two an inhibiting effect on OA. Due to heterogeneity in the test results for cheese, a random IVW representation was used. The results of sensitivity analysis showed no significant heterogeneity or horizontal pleiotropy in the selected SNPS, demonstrating the reliability of Mendelian randomization analysis.ConclusionThis study identified coffee, peas, watercress, and cheese as food items that may have significant dietary effects on osteoarthritis. This information may be useful to consider in the development of OA management strategies.

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

Abstract High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Abstract Background With the emergence of the gig economy as a new economic form, the influence of algorithmic technology control on gig workers’ perceptions and engagement has become a topic of academic concern. This study explores the emotional impact of perceived algorithmic control on gig workers and how it affects their work engagement. Methods This study takes gig workers as the research object to build a structural equation model. Based on the background of gig economy and the Job Demands-Resources model, this paper constructs a mechanism model of the influence of perceived algorithmic control on the work engagement of gig workers. The research data in this paper are collected by questionnaire, and the research hypothesis is tested by the SEM structural model. Results The gig workers in this study believed that perceived algorithmic control positively affects employee work engagement. In addition, burnout was positively correlated with employee work engagement. Burnout played a partial mediating role in the relationship between perceived algorithmic control and employee work engagement. And flow experience played a moderating role through the indirect effect of burnout on employees’ work engagement. Conclusion Perceived algorithmic control causes burnout among gig workers, but strong algorithmic technology support provides them with rich work resources that can help them meet their work needs. That is, the gig workers may still demonstrate a high level of work engagement even if they experience burnout symptoms.

BackgroundDeclining cognitive function (CF) and physical function (PF) relate to poorer health-related quality of life (HRQoL) in older adults. As health literacy (HL) facilitates health information utilization, it may mediate links between functionality and HRQoL appraisals. This study examined HL as an intermediary between joint CF and PF contributions and HRQoL in Hong Kong older adults.Methods490 older adults aged 50–80 years completed assessments from March to July 2021. Health Literacy Survey Questionnaire Short Form 12 questions (HLS-SF12), Montreal Cognitive Assessment (MoCA), Senior Fitness Test (SFT) and 12-Item Short-Form Health Survey version 2 (SF-12v2) were used to assess HL, CF, PF and HRQoL, respectively. Path analysis tested a model with HL mediating CF/PF predictors and HRQoL outcome.ResultsResults for direct effects indicated that CF significantly associated with PF (β = 0.115, SE = 0.012, p

Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.

The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial, directional and controllable differentiation of mesenchymal stem cells (MSCs) into cartilage and bone compartments. Emerging organoid technology offers new opportunities for osteochondral regeneration. In this study, we developed gelatin-based microcryogels customized using hyaluronic acid (HA) and hydroxyapatite (HYP), respectively for inducing cartilage and bone regeneration (denoted as CH-Microcryogels and OS-Microcryogels) through in vivo self-assembly into osteochondral organoids. The customized microcryogels showed good cytocompatibility and induced chondrogenic and osteogenic differentiation of MSCs, while also demonstrating the ability to self-assemble into osteochondral organoids with no delamination in the biphasic cartilage-bone structure. Analysis by mRNA-seq showed that CH-Microcryogels promoted chondrogenic differentiation and inhibited inflammation, while OS-Microcryogels facilitated osteogenic differentiation and suppressed the immune response, by regulating specific signaling pathways. Finally, the in vivo engraftment of pre-differentiated customized microcryogels into canine osteochondral defects resulted in the spontaneous assembly of an osteochondral unit, inducing simultaneous regeneration of both articular cartilage and subchondral bone. In conclusion, this novel approach for generating self-assembling osteochondral organoids utilizing tailor-made microcryogels presents a highly promising avenue for advancing the field of tissue engineering.

Background Neuroarthropathy of the knee or Charcot knee, leading to chronic joint destruction, is a rare disease that is difficult to diagnose. The treatment of this condition is difficult and controversial. Case Presentation A 74‐year‐old Asian woman has had bilateral knee pain for 22 years and deformity for 10 years, which has been aggravating for 2 months. Physical examination showed bilateral knee varus deformity greater than 15°, and −20 to 90° range of motion. X‐ray revealed bilateral varus deformity with massive free body hyperplasia. Combined with medical history as syringomyelia, the patient was diagnosed with bilateral Charcot knees and bilateral joint replacements were performed using Legacy Constrained Condylar Knee prostheses (LCCK; Zimmer, USA). The patient reported satisfactory treatment outcomes, pain relief, and improved range of motion in both knees, without postoperative complications or prosthesis loosening at 2 year after operation. Conclusions Total knee arthroplasty (TKA) may be considered a viable option for treating the Charcot knee. The use of constrained condylar prostheses can produce satisfactory results. Attention should be given to survival risks, complications, and other potential determining factors associated with TKA when devising a treatment strategy for the Charcot knee.

Abstract Background Joint contracture causes a decrease in range of motion (ROM), which severely affects activities of daily living of patients. We have investigated the effectiveness of a multidisciplinary rehabilitation on joint contracture by rat model. Methods We used 60 Wistar rats in this study. The rats were divided into five groups as follows: group 1 was the normal control group; except the group 1, we created left hind limb knee joint contracture using Nagai method for other four groups. The joint contracture modeling group 2 was the model control group for monitoring the spontaneous recovery, and other three groups were given different rehabilitation treatments; for example, group 3 was treadmill running group; group 4 was medication group; group 5 was treadmill running plus medication group. The left hind limbs knee joint ROM and the femoral blood flow indicators (FBFI) including PS, ED, RI, and PI were measured right before and after the 4 weeks of rehabilitation. Result After 4 weeks of rehabilitation treatments, the measured values of ROM and FBFI are compared with the corresponding values of group 2. Firstly, we did not see clear difference in the values of ROM and FBFI for group 2 before and after 4 weeks spontaneous recovery. The improvement of left lower limb ROM for group 4 and group 5 as compared to the group 2 was statistically significant (p

Objective Prosthetic joint infection (PJI) is the main reason of failure of total joint arthroplasty (TJA). This study aimed to investigate the global trends and network visualization in research of PJI. Methods Publications in PJI search during 1980–2022 were extracted from the Science Citation Index‐Expanded of Web of Science Core Collection database (WoSCC). The source data was investigated and analyzed by bibliometric methodology. For network visualization, VOS viewer and R software was used to perform bibliographic coupling, co‐citation, co‐authorship and co‐occurrence analysis and to predict the publication trends in PJI research. Results There were 7288 articles included. The number of publications and relative research interests increased gradually per year globally. The USA made the highest contributions in the world and with the highest H‐index and the most citations. Journal of Arthroplasty published the highest number of articles in this area. The Mayo Clinic, Thomas Jefferson University (Rothman Institute), Hospital Special Surgery and the Rush University were the most contributive institutions by network visualization. Included studies were divided into four clusters: bacterial pathogenic mechanism and antibacterial drugs study, TJA complications, risk factors and epidemiology of PJI, diagnosis of PJI, and revision surgical management. More articles in PJI could be published over the next few years. Conclusion The number of publications about PJI will be increasing dramatically based on the global trends and network visualization. The USA made the highest contributions in PJI. Diagnosis and revision management may be the next hot spots in this field.

BackgroundCardiovascular diabetology is an emergent field focusing on all aspects of diabetes/cardiovascular interrelationship and metabolic syndrome. High-quality evidence needs to be provided to determine the efficacy and safety of interventions in cardiovascular diabetology. The heterogeneity of outcomes among trials limits the comparison of results, and some outcomes are not always meaningful to end-users. The cardiovascular diabetology core outcome set (COS) study aims to develop a COS of interventions for cardiovascular diabetology. In this paper, we introduce the methodological framework for developing the COS.MethodsThe COS development will include the following steps: (a) establish the COS groups of stakeholders, including international steering committee, Delphi survey group, and consensus meeting group; (b) systematic reviews of outcomes used in trials of cardiovascular diabetology; (c) semistructured interview of stakeholders for outcomes of cardiovascular diabetology; (d) generate a list of candidate outcomes and determine the original outcome pool; (e) Delphi survey with stakeholders of cardiovascular diabetology to select potential core outcomes; and (f) review and endorse the cardiovascular diabetology COS by expert consensus meeting.ConclusionsThis current study reports the methodological framework to develop a COS in cardiovascular diabetology and will provide evidence for the future development of COS in cardiovascular diabetology.

Abstract Osteoporotic tendon‐to‐bone healing (TBH) after rotator cuff repair (RCR) is a significant orthopedic challenge. Considering the aligned architecture of the tendon, inflammatory microenvironment at the injury site, and the need for endogenous cell/tissue infiltration, there is an imminent need for an ideal scaffold to promote TBH that has aligned architecture, ability to modulate inflammation, and macroporous structure. Herein, a novel macroporous hydrogel comprising sodium alginate/hyaluronic acid/small extracellular vesicles from adipose‐derived stem cells (sEVs) (MHA‐sEVs) with aligned architecture and immunomodulatory ability is fabricated. When implanted subcutaneously, MHA‐sEVs significantly improve cell infiltration and tissue integration through its macroporous structure. When applied to the osteoporotic RCR model, MHA‐sEVs promote TBH by improving tendon repair through macroporous aligned architecture while enhancing bone regeneration by modulating inflammation. Notably, the biomechanical strength of MHA‐sEVs is approximately two times higher than the control group, indicating great potential in reducing postoperative retear rates. Further cell‐hydrogel interaction studies reveal that the alignment of microfiber gels in MHA‐sEVs induces tenogenic differentiation of tendon‐derived stem cells, while sEVs improve mitochondrial dysfunction in M1 macrophages (Mφ) and inhibit Mφ polarization toward M1 via nuclear factor‐kappaB (NF‐κb) signaling pathway. Taken together, MHA‐sEVs provide a promising strategy for future clinical application in promoting osteoporotic TBH.

AbstractBackground: Copy number variants of uncertain significance (VUS) has brought much distress for patients and great counselling challenges for clinicians. Of these, a special type of VUS (HT-VUS), harbouring one or both breakpoints within the established haploinsufficient or triplosensitive genes, were considered to be more likely to cause clinical effects compared with other types of VUS.Methods: We retrospectively evaluated the properties and clinical significance of those HT-VUS samples in clinical testing for chromosome microarray analysis (CMA).Results: A total of 7150 samples were selected for HT-VUS screening, and 75 (1.05%) subjects with 75 HT-VUS were found. The majority of these HT-VUS were heterozygous duplications and chromosome X had the most HT-VUS. The prevalence of HT-VUS was 0.90% (28/3116) for prenatal low-risk samples, 1.18% (26/2196) for prenatal high-risk samples, 1.37% (10/728) for postnatal samples and 0.99% (11/1110) for early pregnancy loss samples. However, the incidence of HT-VUS was not statistically different between different groups.Conclusions: HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons (either the first or last exons) might be clinically neutral. Our study will be helpful for both interpretation and genetic counselling in the future.

Abstract Background Both the crystalline and soluble forms of cholesterol increase macrophage secretion of interleukin 1β (IL-1β), aggravating the inflammatory response in atherosclerosis (AS). However, the link between cholesterol and regulatory T cells (Tregs) remains unclear. This study aimed to investigate the effect of cholesterol treatment on Tregs. Methods Differentiation of induced Tregs (iTregs) was analyzed using flow cytometry. The expression of hypoxia-inducible factor-1a (HIF-1a) and its target genes was measured by western blotting and/or RT-qPCR. Two reporter jurkat cell lines were constructed by lentiviral transfection. Mitochondrial function and the structure of natural Tregs (nTregs) were determined by tetramethylrhodamine (TMRM) and mitoSOX staining, Seahorse assay, and electron microscopy. The immunoregulatory function of nTregs was determined by nTreg-macrophage co-culture assay and ELISA. Results Cholesterol treatment suppressed iTreg differentiation and impaired nTreg function. Mechanistically, cholesterol induced the production of mitochondrial reactive oxygen species (mtROS) in naïve T cells, inhibiting the degradation of HIF-1α and unleashing its inhibitory effects on iTreg differentiation. Furthermore, cholesterol-induced mitochondrial oxidative damage impaired the immunosuppressive function of nTregs. Mixed lymphocyte reaction and nTreg-macrophage co-culture assays revealed that cholesterol treatment compromised the ability of nTregs to inhibit pro-inflammatory conventional T cell proliferation and promote the anti-inflammatory functions of macrophages. Finally, mitoTEMPO (MT), a specific mtROS scavenger, restored iTreg differentiation and protected nTreg from further deterioration. Conclusion Our findings suggest that cholesterol may aggravate inflammation within AS plaques by acting on both iTregs and nTregs, and that MT may be a promising anti-atherogenic drug.

Abstract Objective To estimate the global prevalence of hip osteoarthritis (HOA) through a systematic review and meta-analysis, and to determine by regression analysis the respective relationships between age and sex, and sex and prevalence. Methods EMBASE, PubMed, Web of science, CINAHL, and SCOPUS were searched from inception until August 2022. Two authors independently extracted data and assessed the quality of the retrieved literature. Random-effects meta-analysis was performed to derive the pooled prevalence. Variations in the prevalence estimate in different subgroups, including diagnostic methods, region, and patient sex, were examined by subgroup meta-analysis. Meta-regression was used to construct the age-specific prevalence of HOA. Results A total of 31 studies were included in our analysis, involving 326,463 participants. Quality evaluation showed that all studies included in the analysis had a Quality Score of at least 4. The most frequently used method for diagnosing HOA was the Kellgren–Lawrence (K-L) grade classification, accounting for 19/31 (61.3%) studies. The pooled prevalence of HOA diagnosed based on the K-L grade ≥ 2 criterion was 8.55% (95% CI 4.85–13.18) worldwide. The prevalence of HOA was lowest in Africa at 1.20% (95% CI: 0.40–2.38), followed by Asia at 4.26% (95% CI 0.02–14.93) and North America at 7.95% (95% CI 1.98–17.36), and highest in Europe at 12.59% (95% CI 7.17–19.25). There was no statistically significant difference in HOA prevalence between men (9.42%, 95% CI:4.81–15.34) and women at (7.94%, 95% CI: 3.57–13.81). The regression model showed a correlation between age and the prevalence of HOA. Conclusion HOA has high prevalence worldwide and increases with age. The prevalence varies significantly by region but not by patient sex. High-quality epidemiological studies are warranted to more accurately estimate the prevalence of HOA.

The Brillouin scattering spectrum has been used to investigate the properties of a liquid medium. Here, we propose an improved method based on the double-edge technique to obtain the Brillouin spectrum of a liquid. We calculated the transmission ratios and deduced the Brillouin shift and linewidth to construct the Brillouin spectrum by extracting the Brillouin edge signal through filtered double-edge data. We built a detection system to test the performance of this method and measured the Brillouin spectrum for distilled water at different temperatures and compared it with the theoretical prediction. The observed difference between the experimental and theoretical values for Brillouin shift and linewidth is less than 4.3 MHz and 3.2 MHz, respectively. Moreover, based on the double-edge technique, the accuracy of the extracted temperatures and salinity is approximately 0.1 °C and 0.5%, respectively, indicating significant potential for application in water detection and oceanography.

Objective Musculoskeletal pain is the most prominent clinical manifestation of more than 150 musculoskeletal disease conditions, and its effective long‐term management poses a great challenge to healthcare systems globally. For this, it is important to understand current research progress on musculoskeletal pain management. The purpose of the present study is to provide a comprehensive insight into the current state of research and global trends in musculoskeletal pain management. Methods Publications on musculoskeletal pain management from 1972 to 2021 were retrieved from the Science Citation Index‐Expanded (SCIE) database. Included articles were any article type related to aspects of musculoskeletal pain management, including etiology, mechanisms, epidemiology, treatment, outcomes, side effects, and patient compliance. Publication data were analyzed using bibliometric methods. The software VOSviewer was employed to perform bibliographic coupling, co‐authorship, co‐citation, and co‐occurrence analysis, and to visualize publication tendencies in musculoskeletal pain management. Results A total of 5475 articles were included in this study. The number of global publications on musculoskeletal pain management has escalated annually. Based on the number of publications and citations from the published literature, as well as the H‐index, the United States led global contributions in this area. The institutions making the highest contributions were the League of European Research Universities (LERU), the University of Sydney, and Harvard University. The journal BMC Musculoskeletal Disorders published the highest number of articles in this area. The published studies fall under six groups: “Prevention and rehabilitation,” “Etiology and diagnosis,” “Clinical study,” “Epidemiology,” “Mental health,” and “Education.” High‐quality primary studies and epidemiology are predicted to be the next prevailing topics in this field of research. Conclusions Based on current global trends, the number of publications on musculoskeletal pain management will continue to increase. Future studies will likely place more emphasis on high‐quality randomized controlled trials (RCTs) and epidemiological studies.

Focal vibratory stimulation (FVS) and neuromuscular electrical stimulation (NMES) are promising technologies for sensory rehabilitation after stroke. However, the differences between these techniques in immediate neuromodulatory effects on the poststroke cortex are not yet fully understood. In this research, cortical responses in persons with chronic stroke (n = 15) and unimpaired controls (n = 15) were measured by whole-brain electroencephalography (EEG) when FVS and NMES at different intensities were applied transcutaneously to the forearm muscles. Both FVS and sensory-level NMES induced alpha and beta oscillations in the sensorimotor cortex after stroke, significantly exceeding baseline levels (p < 0.05). These oscillations exhibited bilateral sensory deficiency, early adaptation, and contralesional compensation compared to the control group. FVS resulted in a significantly faster P300 response (p < 0.05) and higher theta oscillation (p < 0.05) compared to NMES. The beta desynchronization over the contralesional frontal–parietal area remained during NMES (p > 0.05), but it was significantly weakened during FVS (p < 0.05) after stroke. The results indicated that both FVS and NMES effectively activated the sensorimotor cortex after stroke. However, FVS was particularly effective in eliciting transient involuntary attention, while NMES primarily fostered the cortical responses of the targeted muscles in the contralesional motor cortex.

Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice.

Abstract Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non‐EV components in clinical samples. Herein, we present a MEmbrane‐Specific Separation and two‐step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin‐coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2‐positive breast cancer, triple‐negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.

Abstract Conn et al. have recently reported circRNA: DNA hybrids (circR loops) to promote oncogenic gene translocations and impair genome stability which drive leukemia. Herein, we will summarize potential molecular mechanisms and discuss clinical significance of uncovering circR loops as endogenous RNA carcinogens.

Abstract The protective effects of peptides on pigs are controversial. In this study, meta-analysis was used to analyze the protective immune response of peptides. The China National Knowledge Infrastructure, PubMed, Wanfang Data, Cochrane Library, Embase, and gray literature sources were searched for FMDV articles published from the inception of the databases to March 2022. Of the 1403 articles obtained, 14 were selected using inclusion criteria. The experimental data on polypeptide vaccines were analyzed using Microsoft Office Home and Student 2019 Software. From the results, polypeptide vaccine doses (PPVDs) ≤ 1 mg offered protection against FMDV in 69.41% pigs lower than World Organization for Animal Health (OIE) standard (75%, 12/16). PPVDs ≥ 2 mg provided protection against FMDV in 97.22% pigs. When the two groups were compared directly, PPVDs ≥ 2 mg (93.75%) was higher than PPVDs ≤ 1 mg (63.16%). PPVDs ≤ 1 mg provided protection 56% pigs and the inactivated vaccine was 93.33% in direct comparison. In conclusion, PPVDs has a dose-dependent protective effect on pigs and PPVDs ≤ 1 mg group was lower than the inactivated vaccines group.

Abstract Background Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear. Methods Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim’s ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim’s ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim’s ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds’ anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock. Results Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski’s rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets. Conclusions The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.

Abstract The essence of enterotypes is stratifying the entire human gut microbiome, which modulates the association between diet and disease risk. A study was designed at the Center of Reproductive Medicine, Shengjing Hospital of China Medical University and Jinghua Hospital of Shenyang. Prevotella and Bacteroides were analyzed in 407 samples of stool, including 178 men with enterotype B (61 normal, 117 overweight/obese) and 229 men with enterotype P (74 normal, 155 overweight/obese). The ratio between Prevotella and Bacteroides abundance, P/B, was used as a simplified way to distinguish the predominant enterotype. In enterotype P group (P/B ≥ 0.01), obesity was a risk factor for a reduced rate of forward progressive sperm motility (odds ratio [OR] 3.350; 95% confidence interval [CI] 1.881–5.966; P

Abstract To investigate the effect of contoured insoles constructed of different insole materials, including Nora Lunalastik EVA, Nora Lunalight A fresh, Pe-Lite, and PORON Medical 4708 with Langer Biomechanics longitudinal PPT arch pads on offloading plantar pressure on the foot of the elderly with Type 1 or 2 diabetes during gait. Twenty-two elderly with Type 1 or 2 diabetes participated in the study. Their plantar pressure was measured by using an insole measurement system, while the participants walked 10 m in their bare feet or used each experimental insole in random order. The plantar surface was divided into four specific regions including the toes, forefoot, midfoot, and rearfoot. The mean peak pressure (MPP) and pressure–time integral (PTI) of ten steps with or without wearing one of the four insoles were analyzed on the dominant foot and the four specific plantar regions. After completion of the activities, the participants scored each insole from 1 (the least comfortable) to 10 (the most comfortable). The analysis of variance (ANOVA) factor of the insoles had significant effects on the MPP (P

Abstract Background This study aimed to explore whether collagen fiber features and collagen type I alpha 1 (COL1A1) are related to the stiffness of breast lesions and whether COL1A1 can predict axillary lymph node metastasis (LNM). Methods Ninety-four patients with breast lesions were consecutively enrolled in the study. Amongst the 94 lesions, 30 were benign, and 64 were malignant (25 were accompanied by axillary lymph node metastasis). Ultrasound (US) and shear wave elastography (SWE) were performed for each breast lesion before surgery. Sirius red and immunohistochemical staining were used to examine the shape and arrangement of collagen fibers and COL1A1 expression in the included tissue samples. We analyzed the correlation between the staining results and SWE parameters and investigated the effectiveness of COL1A1 expression levels in predicting axillary LNM. Results The optimal cut-off values for Emax, Emean, and Eratio for diagnosing the benign and malignant groups, were 58.70 kPa, 52.50 kPa, and 3.05, respectively. The optimal cutoff for predicting axillary LNM were 107.5 kPa, 85.15 kPa, and 3.90, respectively. Herein, the collagen fiber shape and arrangement features in breast lesions were classified into three categories. One-way analysis of variance (ANOVA) showed that Emax, Emean, and Eratio differed between categories 0, 1, and 2 (P 0.145 was considered the cut-off value, and its efficacy in benign and malignant breast lesions was 0.808, with a sensitivity of 66% and a specificity of 90%. Furthermore, when the COL1A1 expression level > 0.150 was considered the cut-off, its efficacy in predicting axillary LNM was 0.796, with sensitivity and specificity of 96% and 59%, respectively. Conclusions The collagen fiber features and expression levels of COL1A1 positively correlated with the elastic parameters of breast lesions. The expression of COL1A1 may help diagnose benign and malignant breast lesions and predict axillary LNM.

Summary: Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

Background Periprosthetic osteolysis is a serious complication following total hip arthroplasty (THA). However, most orthopedic surgeons only focus on bone loss and hip reconstruction. Thus, it was required to understand the treatment algorithm for periprosthetic osteolysis integrally. Case Presentation A 52‐year‐old Asian male presented with chronic hip pain. A mass appeared on the medial side of the proximal left thigh at more than 20 years after bilateral THA. Radiographs revealed catastrophic periprosthetic osteolysis, especially on the acetabular side. Large amounts of necrotic tissue and bloody fluids were thoroughly debrided during revision THA. A modular hemipelvic prosthesis was used for revision of the left hip. Four years later, the patient presented with right hip pain, where a mass appeared on the medial side of the proximal right thigh. A primary acetabular implant with augment was used for revision of the right hip. Laboratory evaluation of bloody fluid retrieved from surgery revealed elevated levels of inflammatory markers. Conclusion Inflammatory responses to polyethylene wear debris can lead to severe bone resorption and aseptic loosening in the long‐term following THA. Therefore, in spite of revision THA, interrupting the cascade inflammatory might be the treatment principle for periprosthetic osteolysis.

ABSTRACT Bacterial vaginosis (BV) is the most common infection of the lower reproductive tract among women of reproductive age, characterized by a depletion of health-associated Lactobacillus and an overgrowth of anaerobes. Metronidazole has been recommended as a first-line therapy for treating BV for decades. Although most cases are cured by the treatment, recurrent infections of BV seriously affect women’s reproductive health. Until now, limited information on the vaginal microbiota has been explored at the species level. Here, we adopted a single molecular sequencing approach for the 16S rRNA gene, named FLAST (full-length assembly sequencing technology), to analyze the human vaginal microbiota that improved species-level resolution for taxonomy and identified microbiota alterations in the vaginal tract in response to treatment with metronidazole. Appling high-throughput sequencing, we identified 96 and 189 novel full-length 16S rRNA gene sequences in Lactobacillus and Prevotella, respectively, which had not previously been reported in vaginal samples. Moreover, we found that Lactobacillus iners was significantly enriched in the cured group before metronidazole treatment, and that was maintained in a high frequency after the treatment, suggesting an important role for this species in response to metronidazole treatment. Our research also highlights the importance of the single-molecule paradigm for progressing the field of microbiology and applying these insights to better understand the dynamic microbiota during BV treatment. Subsequent novel treatment approaches should be proposed to improve BV treatment outcomes, optimize the vaginal microbiome, and reduce gynecological and obstetric sequelae. IMPORTANCE Bacterial vaginosis (BV) is a common infectious disease of the reproductive tract. Metronidazole treatment, as the first line of treatment, frequently fails at recovery of the microbiome. However, the precise types of Lactobacillus and other bacteria involved in BV remain unclear, and this has resulted in a failure to identify potential markers to predict clinic outcomes. In this study, we adopted a 16S rRNA gene full-length assembly sequencing technology for the taxonomy analysis and evaluation of vaginal microbiota before and after treatment with metronidazole. We additionally identified 96 and 189 novel 16S rRNA gene sequences in Lactobacillus and Prevotella species, respectively, in vaginal samples, which improves our understanding of the vaginal microbiota. Moreover, we found that the abundance of Lactobacillus iners and Prevotella bivia before treatment was associated with a lack of cure. These potential biomarkers will help to facilitate future studies aimed at improving BV treatment outcomes, optimize the vaginal microbiome, and reduce adverse sexual and reproductive outcomes.

ObjectiveThis study assessed the impact of the cervical microbiome on reproductive outcomes in frozen embryo transfer (FET) patients.Study designThis cross-sectional study included 120 women (aged 20–40 years) undergoing FET. A cervical sample obtained before embryo transfer was analyzed using 16S full-length assembly sequencing technology (16S-FAST), which detects full length 16S rDNA.ResultsWe found that >48% of the identified Lactobacillus species were novel. The cervical microbiome was clustered into three cervical microbiome types (CMT): CMT1, dominated by L. crispatus; CMT2, dominated by L. iners; and CMT3, dominated by other bacteria. CMT1 had a significantly higher biochemical pregnancy rate (P=0.008) and clinical pregnancy rate (P=0.006) than CMT2 and CMT3. Logistic analysis showed that compared to CMT1, CMT2 and CMT3 were independent risk factors for biochemical pregnancy failure (odds ratio [OR]: 6.315, 95% confidence interval [CI]: 2.047-19.476, P=0.001; OR: 3.635, 95% CI: 1.084-12.189, P=0.037) and clinical pregnancy failure (OR: 4.883, 95% CI: 1.847-12.908, P=0.001; OR: 3.478, 95% CI: 1.221-9.911, P=0.020). A L. crispatus-dominated group as a diagnostic indicator of biochemical and clinical pregnancy positive had area under the curve (AUC) values of 0.651(P=0.008) and 0.645(P=0.007), respectively. Combining the cervical microbiome with embryonic stage optimized the diagnostic performance for biochemical and clinical pregnancy failure with AUC values of 0.743(P

Magnaporthe oryzae Oryzae (MoO) pathotype is a devastating fungal pathogen of rice; however, its pathogenic mechanism remains poorly understood. The current research is primarily focused on single-omics data, which is insufficient to capture the complex cross-kingdom regulatory interactions between MoO and rice. To address this limitation, we proposed a novel method called Weighted Gene Autoencoder Multi-Omics Relationship Prediction (WGAEMRP), which combines weighted gene co-expression network analysis (WGCNA) and graph autoencoder to predict the relationship between MoO–rice multi-omics data. We applied WGAEMRP to construct a MoO–rice multi-omics heterogeneous interaction network, which identified 18 MoO small RNAs (sRNAs), 17 rice genes, 26 rice mRNAs, and 28 rice proteins among the key biomolecules. Most of the mined functional modules and enriched pathways were related to gene expression, protein composition, transportation, and metabolic processes, reflecting the infection mechanism of MoO. Compared to previous studies, WGAEMRP significantly improves the efficiency and accuracy of multi-omics data integration and analysis. This approach lays out a solid data foundation for studying the biological process of MoO infecting rice, refining the regulatory network of pathogenic markers, and providing new insights for developing disease-resistant rice varieties.

Abstract Purpose The purpose of this review was to synthesize the empirical evidence of relevant studies related to preventive behaviors in response to the COVID-19 pandemic among children and adolescents. Further to this, we aimed to identify the demographic, psychological, and social and environmental correlates of such behaviors. Methods Following PRISMA guidelines, eligible literature was identified by searching seven databases (PsycINFO, PubMed, MEDLINE, EMBASE, Cochrane Library, PROSPERO registry platform, and ClinicalTrials.gov website) and reference list of included studies and relevant review papers from 1st Jan 2020 to 28th Feb 2021. The standardized mean difference and correlation coefficients r were extracted to estimate the effect sizes. Analyses were conducted using R software. Results Of the 35,271 original papers, 23 eligible studies were included in the qualitative synthesis and all these studies were of moderate-to-high quality, of which 17 studies were further included into the quantitative analysis. Children and adolescents (6–20 yrs.) showed a poorer practice of COVID-19 preventive behaviors compared to younger adults (21–59 yrs.) with a small-to-medium effect size (SMD = -.25, 95%CI = -.41 to -.09). For the demographic correlates, children and adolescents’ COVID-19 preventive practice was found to be significantly associated with gender (r = .14, 95%CI = .10 to .18), while not with age (r = -.02, 95%CI = -.14 to .10). Narratively, knowledge was found to be consistently and significantly correlated. For the psychological correlates, small-to-medium overall effects were identified for the association with attitudes (r = .26, 95%CI = .21 to .31) and perceived severity (r = .16, 95%CI = .01 to .30). For the family and social correlates, a non-significant association was identified between family economic status and COVID-19 preventive behaviors (r = .004, 95%CI = -.12 to .12). Conclusions Interventions and relevant policies of promoting children and adolescent’s preventive measures should be a priority. Further, empirical studies identifying the demographic, psychological, and family and social correlates of children and adolescents’ preventive behaviors are needed.

Abstract Background The elderly population worldwide is increasing exponentially which will be associated with more people suffering from cognition and fitness declines. The well-established benefits of exercise training for the elderly’s cognitive and physical functioning have been observed. However, the amalgamated effect of combining cognitive and physical exercises on the older adults’ cognitive functions, physical fitness, or psycho-related health remains unclear. Thus, this study protocol was planned to conduct different combinations of cognitive and/or physical training interventions to community-dwelling older adults and expected to see the multifaceted effects of the varied combination of training on their health. Methods This study is a cluster randomized controlled trial (CRCT). A total of 285 older adults (age ≥ 60) from twenty elderly centres as clusters will be randomly selected and assigned to intervention groups (IGs, n = 16) or control groups (CGs, n = 4). Each IG will be randomly assigned to one of the four combinations of three training modes that include cognitive (A), physical (B), and combined cognitive and physical training (CCPT, i.e. C), namely Mixed ABC, A + B, C + A, B + C. The intervention will last for 4 months in which the training is conducted for 16 sessions, 2 sessions per week, and 60 min per session. Four repeated assessments (pre-test, two post-training tests after 2 months and 4 months, and a follow-up test) will be conducted. The CG will only receive the four repeated assessments but no intervention. The outcome measures include cognitive tests (tests of execution, memory, and psych-social status), physical fitness, and dynamic balance tests. Discussion This study will provide substantial evidence that the integrated format of cognitive and physical exercises training will have higher cognition and fitness impact than the single training modes, and all these mixed modalities will have greater positive outcomes than the control condition. If the effectiveness is proven, the intervention can be further explored and extended to the nation so that many more elderly would be benefited. Trial registration The trial has been registered in the ClinicalTrials.gov in U.S. NIH (ID: NCT04727450 , date: January 27, 2021).

Abstract Carbon dots (CDs) with excellent cytocompatibility, tunable optical properties, and simple synthesis routes are highly desirable for use in optical bioimaging. However, the majority of existing CDs are triggered by ultraviolet/blue light, presenting emissions in the visible/first near‐infrared (NIR‐I) regions, which do not allow deep tissue penetration. Emerging research into CDs with NIR‐II emission in the red region has generated limited designs with poor quantum yield, restricting their in vivo imaging applications due to low penetration depth. Developing novel CDs with NIR‐II emissions and high quantum yield has significant and far‐reaching applications in bioimaging and photodynamic therapy. Here, it is developed for the first time Fe‐doped CDs (Fe‐CDs) exhibiting the excellent linear relationship between 900–1200 nm fluorescence‐emission and pH values, and high quantum yield (QY‐1.27%), which can be used as effective probes for in vivo NIR‐II bioimaging. These findings demonstrate reliable imaging accuracy in tissue as deep as 4 mm, reflecting real‐time pH changes comparable to a standard pH electrode. As an important example application, the Fe‐CDs probe can non‐invasively monitor in vivo gastric pH changes during the digestion process in mice, illustrating its potential applications in aiding imaging‐guided diagnosis of gastric diseases or therapeutic delivery.

Cyclommatus stag beetles (Coleoptera, Lucanidae) are very interesting insects, because of their striking allometry (mandibles can be longer that the whole body in large males of some species) and sexual dimorphism. They mainly inhabit tropical and subtropical forests in Asia. To date, there has been no molecular phylogenetic research on how these stag beetles evolved and diversified. In this study, we constructed the first phylogenetic relationship for Cyclommatus using multi-locus datasets. Analyses showed that Cyclommatus is monophyletic, being subdivided into two well-supported clades (A and B). The clade A includes the island species from Southeast Asia, and the clade B is formed by the continental species. The divergent time estimates showed these beetles split from the outgroup around 43.10 million years ago (Mya) in the late Eocene, divided during the late Oligocene (around 24.90 Mya) and diversified further during the early and middle Miocene (around 18.19 Mya, around 15.17 Mya). RASP analysis suggested that these beetles likely originated in the Philippine archipelago, then dispersed to the other Southeast Asian archipelagoes, Indochina Peninsula, Southeast Himalayas, and Southern China. Moreover, relatively large genetic distance and stable morphological variations signified that the two clades reach the level of inter-generic differences, i.e., the current Cyclommatus should be separated in two genera: Cyclommatus Parry, 1863 including the clade A species, and Cyclommatinus Didier, 1927 covering the clade B species. In addition, the evidence we generated indicated these beetles’ diversification was promoted probably by both long-distance dispersal and colonization, supporting an “Upstream” colonization hypothesis. Our study provides insights into the classification, genetics and evolution of stag beetles in the Oriental region.

Purpose. To evaluate the prognosis of patients with benign phyllodes tumors (PTs) treated by different surgical methods and to explore the influencing factors of local recurrence. Methods. We retrospectively analyzed 215 benign PTs from 193 patients who underwent surgery at Chinese PLA General Hospital between October 2008 and December 2020. We stratified our analysis according to surgical factors and explored the clinicopathological factors to influence local recurrence. Results. Among 193 patients, a total of 17 (8.8%, 17/193) recurred during follow-up. There were 89 patients in the US-VAE group, of whom 6 (6.7%) recurred; 8 of 57 patients (14%) in the local lumpectomy group recurred, while 3 of 47 patients (6.4%) in the extended lumpectomy group recurred (P=0.252). Multivariate logistic regression analysis showed that tumor diameter, mitosis, and history of breast myoma were independent risk factors for tumor recurrence (P=0.005, P=0.006, and P=0.004, respectively). The intraoperative blood loss, operation time, and scar length of the US-VAE group were shorter than those of the other two groups (P10 mm. Therefore, we recommend that a follow-up observation policy be adopted for patients with unexpected benign PTs, rather than unnecessary open surgical resection. Patients’ maximum tumor diameter, mitosis, and fibroadenoma history were independent predictors for recurrence of benign PTs.

Metabolites of Emericella nidulans (EN) were separated by chromatographic methods from crude hexane included emericellin and sterigmatocystin, while crude ethyl acetate found demethylsterigmatocystin. These metabolites proved to be antagonistic to Magnaporthe oryzae, the causal agent of rice blast. Crude extracts and nano-particles derived from EN inhibited M. oryzae. The ethyl acetate crude extract derived inhibited M. oryzae with an effective dose (ED50) of 66 μg/mL. The nanoparticles showed better inhibition of M. oryzae than crude extracts at low concentrations. Nanoparticles, namely from crude ethyl acetate, crude methanol and crude hexane of EN were active against M. oryzae with ED50 of 4.2 μg/mL, 4.5 μg/mL, 8.9 μg/mL, respectively. It detected sakuranetin (rate of flow value is 0.09) in nano-EN treated rice leaves. These nanoparticles inhibited M. oryzae and acted as a new elicitor to induce immunity.