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Abstract Introduction Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function. Methods Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group. Results Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups. Conclusions Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore.

Abstract Currently, in vitro cultured corneal epithelial transplantation is effective in treating limbal stem cell dysfunction (LSCD). Selecting carriers is crucial for constructing the corneal epithelium through tissue engineering. In this study, the traditional amniotic membrane (AM) was modified, and mesenchymal stem cells (MSCs) were inoculated into the ultra-thin amniotic membrane (UAM) stroma to construct a novel UAM-MSC tissue-engineered corneal epithelial carrier, that could effectively simulate the limbal stem cells (LSCs) microenvironment. The structure of different carriers cultured tissue-engineered corneal epithelium and the managed rabbit LSCD model corneas were observed through hematoxylin–eosin staining. Cell phenotypes were evaluated through fluorescence staining, Western blotting, and RT-qPCR. Additionally, cell junction genes and expression markers related to anti-neovascularization were evaluated using RT-qPCR. Corneal epithelium cell junctions were observed via an electron microscope. The tissue-engineered corneal epithelium culture medium was analyzed through mass spectrometry. Tissue-engineered corneal epithelial cells expanded by LSCs on UAM-MSCs had good transparency. Simultaneously, progenitor cell (K14, PNCA, p63) and corneal epithelial (PAX6) gene expression in tissue-engineered corneal epithelium constructed using UAM-MSCs was higher than that in corneal epithelial cells amplified by UAM and de-epithelialized amniotic membrane. Electron microscopy revealed that corneal epithelial cells grafted with UAM-MSCs were closely connected. In conclusion, the UAM-MSCs vector we constructed could better simulate the limbal microenvironment; the cultured tissue-engineered corneal epithelium had better transparency, anti-neovascularization properties, closer intercellular connections, and closer resemblance to the natural corneal epithelial tissue phenotype.

Abstract Background and purpose This study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high‐dose radiation prior to or during systemic therapy at a single academic institution. Methods We identified patients with metastatic melanoma who underwent high‐dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan‐Meier method, we plotted overall survival (OS), progression‐free survival‐1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors. Results We analyzed 34 patients with 79 lesions, with a median follow‐up of 17.4 months. Sixty‐eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first‐line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST. Conclusion HDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits.

Plant anatomy is patterned early during leaf development which suggests studying the spatial–temporal transcriptomes of primordia will help identify critical regulative and functional genes. We successfully isolated the leaf primordia tissues from the C3 grass rice and the C4 grass foxtail millet by laser capture microdissection (LCM) and studied the gene expression throughout leaf developmental stages. Our data analysis uncovered the conserved expression patterns of certain gene clusters both in rice and foxtail millet during leaf development. We revealed genes and transcription factors involved in vein formation, stomatal development, and suberin accumulation. We identified 79 candidate genes associated with functional regulation of C4 anatomy formation. Screening phenotype of the candidate genes revealed that knock-out of a putative polar auxin transport related gene NAL1 resulted significantly reduced veinal space in rice leaf. Our present work provides a foundation for future analyses of genes with novel functions in grasses and their role in leaf development, in particular the role in leaves with a contrasting C3 vs. C4 biosynthetic pathway.

Abstract Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic improvement. Currently available genome-editing tools have a limited number of targets, restricting their application in genetic research. In this study, we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors, eight donor vectors, four destination vectors, and one primer-design software package. By combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sgRNA expression cassettes, the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci. A rice knockout vector containing 49 sgRNA expression cassettes was assembled and a high co-editing efficiency was observed. This plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.

Objective: To formulate an efficacious radioprotective combination of Chinese medicines with minimal toxicity. Methods: Aqueous and alcoholic extracts from 38 traditional Chinese herbs were prepared. To produce drug-containing sera, rats received six doses of each extract via oral gavage at 12-h intervals. Subsequently, human lung epithelial BEAS-2B cells were cultured in these drug-containing sera. The cell viability was assessed after different doses of irradiation to identify the radioprotective effects of Chinese herbal extracts. The efficacy of a selected Chinese herbal extract combination was further confirmed through cell viability analysis via in vitro colony formation and survival rate assessments in C57BL/6 mice post-irradiation. Results: Extracts from Angelicae Sinensis Radix (ASR; two extracts), Citri Reticulatae Pericarpium (CRP), Platycladi Cacumen (PC), Schisandrae chinensis Fructus (SF), Scutellariae Radix (SR), and Glycyrrhizae Radix et Rhizome (GRR) demonstrated radioprotective effects. The combination of the seven Chinese herbal extracts notably increased the survival and viability of the BEAS-2B cells exposed to varying doses of X-rays. Moreover, the group of mice receiving Chinese medicine combination and irradiation exhibited prolonged survival after exposure to 6.5 ​Gy X-rays with a median survival of （14 ​± ​2）d compared to （11 ​± ​2）d in the irradiated group without the herbal treatment. Additionally, the Chinese medicine combination group displayed a significantly higher 28 ​d survival rate (30%) compared to the irradiation-only group (16.6%, P ​

Endometrial large cell neuroendocrine carcinoma (LCNEC) is a highly malignant tumor that presents with neuroendocrine function. It is difficult to diagnose at an early stage. Moreover, the diagnosis depends on the pathological and immunohistochemical findings. It is also prone to distant metastasis, but is difficult to treat and shows poor prognosis. Presently, there exists no unified treatment plan, and the prognosis of this disease is also poor. We reported here an analysis and literature review of a case of endometrial LCNEC to facilitate the comprehension of this disease and provide help toward clinical diagnosis and treatment.

IntroductionA series of functional disorders commonly occur after stroke, of which upper limb dysfunction is the most difficult to recover. The upper limb rehabilitation effect of Tai Chi Yunshou(TCY) in the later stage of stroke has been confirmed by research. Body weight support-Tai Chi Yunshou (BWS-TCY) is based on TCY exercise and robotic exoskeletons offers most flexibility in deweighting and control strategy. This study is aimed to explore the effect of BWS-TCY on upper limb motor function in stroke based on neurobiomechanics.Methods and analysisA single-blind randomized controlled trial will be conducted on 36 stroke survivors who will be randomly assigned to three groups: experimental group, control group A and control group B. In addition, 12 healthy elderly people will be recruited into the healthy control group. Those in the experimental group will receive 20 min of CRT and 20 min of BWS-TCY training, while participants in the control group A will receive 20 min of CRT and 20 min of Robot-assisted training. Participants in the control group B will undergo 40 min of Conventional rehabilitation training (CRT) daily. All interventions will take place 5 days a week for 12 weeks, with a 12-week follow-up period. No intervention will be carried out for the healthy control group. Upper limb function will be assessed before and after the intervention using various rating scales (Fugl-Meyer Assessment, Wolf Motor Function Test, etc.), as well as neurobiomechanical analyses (surface electromyography, functional near-infrared brain function analysis system, and Xsens maneuver Capture System). Additionally, 10 healthy elderly individuals will be recruited for neurobiomechanical analysis, and the results will be compared with those of stroke survivors.DiscussionThe results of this study will offer initial evidence on the effectiveness and feasibility of BWS-TCY as an early intervention for stroke rehabilitation. Positive findings from this study could contribute to the development of guidelines for the use of BWS-TCY in the early stages of stroke.Ethics and disseminationThis study has been approved by the Research Ethics Committees of the seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Study ID: 2022-7th-HIRB-022). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences.Clinical trial registrationhttps://clinicaltrials.gov/, ChiCTR 2200063150.

Abstract Background Low-grade Fibromyxoid Sarcoma(LGFM)is a rare fibrosarcoma, which mainly occurs in young people and is mostly seen in the trunk and limbs. The tumor is usually FUS-CREB3L2 fusion caused by t(7;16)(q32-34;p11)chromosome translocation, and rarely FUS-CREB3L1 and EWSR1-CREB3L1 fusion. MUC4 diffuse strong positive can be used as a specific index of LGFM. LGFM is similar to Sclerosing Epithelioid Fibrosarcoma(SEF) and may have the same origin. Case presentation We report a case of LGFM in the chest wall. A female who is 59 years old. In 2016, CT showed dense nodule shadow and focal thickening of the left pleura, the patient underwent surgery, Pathological report that low to moderate malignant fibrosarcoma(fibromyxoid type). The CT re-examination in 2021 showed that the tumors on the left chest wall were significantly larger than before. Pathological examination showed the disease is composed of alternating collagen like and mucinous areas. Under high-power microscope, the tumor cells are consistent in shape, spindle or short spindle, and the tumor cells are arranged in bundles. In local areas, the density of tumor cells is significantly increased, mixed with collagen fibers, and small focal SEF appear. The result of immunohistochemistry showed that SMA, Desmin, CD34, STAT6, S100, SOX10, HMB45 and Melan A were negative, EMA was weakly positive, MUC4 was diffuse and strongly positive, and Ki67 index was low (3%). Conclusion Sequencing results showed that MET, EGFR, KMT2B and RET gene were mutated in LGFM, and KMT2B gene had cancer promoting effect, but there was no literature report in LGFM, which may be of certain significance for the diagnosis and treatment of LGFM.

Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.

As a typical strongly correlated transition oxide, vanadium dioxide (VO2) based nanomaterials have drawn many research attentions these years due to the giant metal-to-insulator phase transition (MIPT) at around 68 °C. However, due to the complexities of the V–O system and interplays between various vanadium oxide phases, the synthesis of high-quality VO2 nanopowders is still fraught with many challenges, especially in air atmosphere. In this paper, we report a novel air atmosphere available liquid-shielding synthesis method for thermochromic VO2 nanoparticles, by using low-eutectic molten-salt (LiCl–KCl) as the liquid-state air-insulation medium at elevated temperature and high-pressure pressed VOSO4–KCl pillars immersed in these liquid salts as the precursor. Small amounts of glucose are added to introduce a slight reductive environment, and well dispersed VO2 nanoparticles with excellent thermochromic properties can be directly synthesized at an ultra-low temperature of 375 °C. This feasible and atmosphere-available mass-production method is rarely reported in the related fields, which may provide a novel protocol strategy for the synthesis of high performance thermochromic VO2 and other functional oxide powders.

In this study, a novel strain with high Na2SeO3 reducing ability was screened from marine strains, providing a new reduction system for the biosynthesis of Se nanoparticles (SeNPs). Firstly, 41 marine strains from Arctic Ocean sediments were screened, and a strain with high selenium-tolerant was obtained and species identified. Subsequently, the screened marine strain was used for the biosynthesis SeNPs and the SeNPs were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and particle size analysis. Furthermore, the antibacterial activities of SeNPs were also determined. The results showed that strain 72 had the strongest tolerance to Na2SeO3, which could grow in the presence of 300 mmol/L Na2SeO3 and reducing it to brick red SeNPs. Subsequently, strain 72 was identified and named as Bacillus sp. Q72. The SeNPs biosynthesized by this strain were spherical particles with an average size of 169.3 nm and a potential of −48.1±0.5 mV. There were amino and hydroxyl groups on their surface. The SeNPs produced by Bacillus sp. Q72 showed better inhibitory activity against E. coli. When the concentration of SeNPs was 200 μg/mL, the inhibitory rate against E. coli reached 92.1%.

Frost formation poses challenges in various sectors, impacting efficiency and safety. Active methods involve energy-consuming processes like heating, while passive approaches utilize protective coatings or hydrophobic surfaces to minimize frost aggregation. However, low thermal conductivity remains a concern. In previous research, lotus leaves inspired micro-meter-sized asperities were effective in controlling frost growth. Applying this concept to plastic, particularly low-cost PVC, raised challenges due to its low thermal conductivity. The study explores utilizing carbon black (CB) waste from hard coating processes to enhance PVC's thermal conductivity, forming a micro-plastic texture (MPT). The research investigates the influence of CB amount and AC voltage frequency on MPT features and thermal conductivity, aiming for a sustainable solution to address frost-related issues. Incorporating 0.9 vol.% CB into PVC solution under a 2 kV AC electric field (6 Hz) resulted in an extensively distributed MPT on the surface. This MPT, formed under the 6 Hz condition, exhibited no in-plane bias, making it an ideal surface for preventing frost formation. Adding CB to PVC within the range of 0 to 2.1 vol.% and applying a 2 kV, 6 Hz AC electric field led to independent MPT formation at concentrations between 0.4 to 1.2 vol.%. Conducting cooling tests in atmospheric and vacuum conditions, we found that MPT with 0.9 vol.% CB displayed a thermal conductivity of approximately 0.19 kW/mK in atmospheric conditions, similar to aluminum alloy. However, with 1.2 vol.% or more CB, it decreased to about 0.15 kW/mK. In vacuum conditions, MPT with 1.2 vol.% CB exhibited a higher thermal conductivity of 0.063 kW/mK compared to the 0.055 kW/mK observed in MPT with 0 vol.% CB.

Summary: Background: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. Methods: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. Findings: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. Interpretation: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. Funding: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

Background Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence.Aim To reduce unnecessary transfusion of albumin.Interventions Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage.Implementation and evaluation Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures.Results Appropriate albumin usage based on indication increased from 30% to 50% (p

The double salient pole structure of Switched Reluctance Motor (SRM) makes its electromagnetic field exist nonlinear saturation characteristics, resulting in its large torque pulsation in operation, so it is difficult to achieve speed regulation smoothly by traditional control methods. In view of this problem, a sliding mode control strategy which is based on synchronous transmission technology was proposed.Firstly, the basic structure of switched reluctance motor was analyzed, and the mathematical model of mechanical motion of switched reluctance motor was established. Secondly, an improved sliding mode controller which is based on synchronous signal transmission technology was designed by analyzing the reason of large torque ripple of switched reluctance motor, and the stability of the system was proved. Finally, simulation is used to verify the effectiveness of the control strategy.Compared with the traditional PID (Proportional Integral Differential) control algorithm, this control technology not only suppresses the SRM torque ripple effectively , but also makes the sliding mode controller output the precise target electromagnetic torque quickly by increasing the control variables. The results of research indicate that this design can not only restrain the torque ripple effectively, but also adjust the convergence speed and overshoot of the controller by adjusting the design parameters.

Abstract Background Recent advances in circulating cell-free DNA (cfDNA) analysis from biofluids have opened new avenues for liquid biopsy (LB). However, current cfDNA LB assays are limited by the availability of existing information on established genotypes associated with tumor tissues. Certain cancers present with a limited list of established mutated cfDNA biomarkers, and thus, nonmutated cfDNA characteristics along with alternative biofluids are needed to broaden the available cfDNA targets for cancer detection. Saliva is an intriguing and accessible biofluid that has yet to be fully explored for its clinical utility for cancer detection. Methods In this report, we employed a low-coverage single stranded (ss) library NGS pipeline “Broad-Range cell-free DNA-Seq” (BRcfDNA-Seq) using saliva to comprehensively investigate the characteristics of salivary cfDNA (ScfDNA). The identification of cfDNA features has been made possible by applying novel cfDNA processing techniques that permit the incorporation of ultrashort, ss, and jagged DNA fragments. As a proof of concept using 10 gastric cancer (GC) and 10 noncancer samples, we examined whether ScfDNA characteristics, including fragmentomics, end motif profiles, microbial contribution, and human chromosomal mapping, could differentiate between these two groups. Results Individual and integrative analysis of these ScfDNA features demonstrated significant differences between the two cohorts, suggesting that disease state may affect the ScfDNA population by altering nuclear cleavage or the profile of contributory organism cfDNA to total ScfDNA. We report that principal component analysis integration of several aspects of salivary cell-free DNA fragmentomic profiles, genomic element profiles, end-motif sequence patterns, and distinct oral microbiome populations can differentiate the two populations with a p value of

Abstract Background The Q-426 strain isolated from compost samples has excellent antifungal activities against a variety of plant pathogens. However, the complete genome of Q-426 is still unclear, which limits the potential application of Q-426. Results Genome sequencing revealed that Q-426 contains a single circular chromosome 4,086,827 bp in length, with 4691 coding sequences and an average GC content of 46.3%. The Q-426 strain has a high degree of collinearity with B. velezensis FZB42, B. velezensis SQR9, and B. amyloliquefaciens DSM7, and the strain was reidentified as B. velezensis Q-426 based on the homology analysis results. Many genes in the Q-426 genome have plant growth-promoting activity, including the secondary metabolites of lipopeptides. Genome mining revealed 14 clusters and 732 genes encoding secondary metabolites with predicted functions, including the surfactin, iturin, and fengycin families. In addition, twelve lipopeptides (surfactin, iturin and fengycin) were successfully detected from the fermentation broth of B. velezensis Q-426 by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC–QTOF–MS/MS), which is consistent with the genome analysis results. We found that Q-426 produced indole-3-acetic acid (IAA) at 1.56 mg/l on the third day of incubation, which might promote the growth of plants. Moreover, we identified eighteen volatile compounds (VOCs, including 2-heptanone, 6-methylheptan-2-one, 5-methylheptan-2-one, 2-nonanone, 2-decanone, 2-undecanone, 2-dodecanone, 2-tridecanone, 2-tetradecanone, 2-nonadecanone, pentadecanoic acid, oleic acid, dethyl phthalate, dibutyl phthalate, methyl (9E,12E)-octadeca-9,12-dienoate), pentadecane, (6E,10E)-1,2,3,4,4a,5,8,9,12,12a-decahydro-1,4-methanobenzo[10]annulene, and nonanal) based on gas chromatograph-mass spectrometer (GC/MS) results. Conclusions We mined secondary metabolite-related genes from the genome based on whole-genome sequence results. Our study laid the theoretical foundation for the development of secondary metabolites and the application of B. velezensis Q-426. Our findings provide insights into the genetic characteristics responsible for the bioactivities and potential application of B. velezensis Q-426 as a plant growth-promoting strain in ecological agriculture.

Abstract Background Molecular testing is critical to guiding treatment approaches in patients with metastatic non‐small cell lung cancer (mNSCLC), with testing delays adversely impacting the timeliness of treatment decisions. Here, we aimed to evaluate the time from initial mNSCLC diagnosis to treatment decision (TTD) following implementation of in‐house EGFR, ALK, and PD‐L1 testing at our institution. Methods We conducted a retrospective chart review of 165 patients (send‐out testing, n = 92; in‐house testing, n = 73) with newly diagnosed mNSCLC treated at our institution. Data were compared during the send‐out (March 2017–May 2019) and in‐house (July 2019–March 2021) testing periods. We performed a detailed workflow analysis to provide insight on the pre‐analytic, analytic, and post‐analytic intervals that constituted the total TTD. Results TTD was significantly shorter with in‐house testing (10 days vs. 18 days, p

Objective: To analyse four cases of intervention via the internal mammary artery–anterior descending branch and provide and summarise the clinical treatment experience. Methods: The clinical data of four patients with distal restenosis of a left anterior descending artery (LAD) anastomosis after left internal mammary artery (LIMA)–LAD bypass surgery, who were admitted to the Gansu Institute of Cardiovascular Diseases between March 2013 and April 2022, were retrospectively analysed and reviewed together with the relevant literature. Results: Among the four patients, one was treated with intracoronary stenting via the internal mammary artery route, two were treated with intracoronary drug-coated balloon dilation (one of whom underwent fractional flow reserve [FFR] testing), and two underwent FFR testing (one of whom had a negative test result until the end of the procedure and continued to take medication during follow-up; the other patient had a positive result and further interventions). There were no deaths or postoperative complications in the group, and the patients were followed up for 4 months to 9 years, with good long-term outcomes. Conclusion: Percutaneous coronary intervention (PCI) via the internal mammary artery route is safe and effective, and patients with anastomotic distal stenosis or anastomotic stenosis of LAD bypass anastomosis may be considered for PCI via the internal mammary artery route.

Summary: Besides traditional ubiquitin-dependent proteasome degradation, thousands of eukaryotic proteins more than previously appreciated could undergo ubiquitin-independent proteasomal degradation (UbInPD). A pathogen-encoded effector protein SAP05 secreted by phytoplasma, could hijack hostage Rpn10 subunit of proteasome derived from Arabidopsis thaliana and target the degradation of GATA BINDING FACTOR (GATA) or SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors (TFs) without ubiquitin or additional proteasome shuttle factors. To explain how could SAP05 target the degradation bypassing the ubiquitin-dependent pathway, we have determined the crystal structure of the complex between Arabidopsis thaliana Rpn10 and Aster Yellows witches'-broom phytoplasma SAP05 or onion yellow phytoplasma SAP05, which showed a previously unknown recognition interface. Sequence alignment and structural biological evidence showed that this interaction is highly conserved in various SAP05 homologs, suggesting a general mode in plant infection. After docking the complex structure to the plant proteasome, SAP05 was near to the adenosine triphosphatase (ATPase) central pore and enough to submit substrate to degradation process, which suggested a molecular glue-like role to bridge TFs close to the ATPase central pore of proteasomes for the direct degradation.

Introduction. To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods. Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results. After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion. Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism.

Motivating active participation in e-commerce logistics alliances to enhance delivery efficiency and customer satisfaction has long been a societal interest. Leveraging the quantum game theory, this paper develops a model for incentivizing collaboration within these alliances. This model enables theoretical and numerical analysis of members’ strategies and entanglement levels. The findings show that quantum strategies increase members’ profits, achieving Nash equilibriums and Pareto optimal outcomes, outperforming the classical game theory. In addition, the size of quantum entanglement emerges as a critical determinant influencing members’ active participation in collaborative distribution. Strengthening information sharing and aligning interests can enhance entanglement levels among members, making them more inclined to adopt strategies promoting active involvement in collaborative distribution. Moreover, members can adapt their strategies based on the initial entanglement in collaborative distribution, thereby incentivizing participation and reducing ethical risks. In conclusion, through numerical analysis, we present relevant strategies and recommendations for incentivizing collaborative distribution within e-commerce logistics alliances.

BackgroundThe correlation between sarcopenia and hematological malignancy prognosis is still controversial. Design: A systematic review and meta-analysis. Objectives: To explore sarcopenia’s prevalence and prognostic value in hematologic malignancies.Data sources and methodsWe searched Embase, MEDLINE, and Cochrane Library through Ovid SP using an appropriate search strategy on August 28, 2022, and updated the search results on January 9, 2023. Study quality was assessed using the Newcastle-Ottawa scale. The pooled prevalence of sarcopenia was calculated with a 95% confidence interval (CI). Relationships between sarcopenia and prognostic value were expressed as hazard ratio (HR) and 95% CI. HR means the probability of something undesirable, i.e., death or disease progression.ResultsThe search identified more than 3992 studies, and 21 (3354 patients, median or mean age ranging from 36 to 78 years) were finally included. The risk of bias in the studies was low to medium. All included studies were diagnosed based on low muscle mass (LMM). Muscle mass was assessed mainly through imaging technologies, and different cut-offs were applied to determine LMM. The prevalence of sarcopenia was 44.5%, which could fluctuate by age. Subgroup analysis showed that older people had a higher sarcopenic rate than the non-elderly group. Sarcopenia resulted in an inferior prognosis [overall survival: HR 1.821, 95% CI 1.415-2.343; progression-free survival: HR 1.703, 95% CI 1.128-2.571).ConclusionSarcopenia has a prevalence of over 30% in malignant hematologic patients and is associated with a poorer prognosis. Future studies with a standardized sarcopenia diagnostic criterion were needed to investigate sarcopenia’s prevalence and prognostic effects in hematologic malignancies.

Abstract Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Recently, there have been several reports that predicted loss of function variants in HSD17B13 protect against the progression of steatosis to non-alcoholic steatohepatitis with fibrosis and hepatocellular carcinoma. Here we report crystal structures of full length HSD17B13 in complex with its NAD+ cofactor, and with lipid/detergent molecules and small molecule inhibitors from two distinct series in the ligand binding pocket. These structures provide insights into a mechanism for lipid droplet-associated proteins anchoring to membranes as well as a basis for HSD17B13 variants disrupting function. Two series of inhibitors interact with the active site residues and the bound cofactor similarly, yet they occupy different paths leading to the active site. These structures provide ideas for structure-based design of inhibitors that may be used in the treatment of liver disease.

Abstract Background Currently, immune checkpoint blockers (ICB) and radiotherapy (RT) combination therapy is broadly applied in non‐small cell lung cancer (NSCLC) patients. However, meta‐analysis about safety and efficacy of RT + ICB versus ICB has not yet been reported. To evaluate safety and efficacy of the combination therapy of ICB and RT in patients with recurrent or metastatic NSCLC and explore factors related to higher response rates, longer lifetime, and lower toxicity, meta‐analysis of previous clinical data will be presented in this article. Methods A literature search on patients with recurrent or metastatic NSCLC treated with RT + ICB versus ICB was performed using the Cochrane Library, Embase and PubMed up to December 10, 2022. Suitable quality assessment checklists were selected corresponding to various types of research studies. Comparative and single‐arm studies were analyzed using Stata 14.0. Results 10 comparative studies and 15 arms of combination therapy were included for this meta‐analysis. RT significantly improved objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and progression‐free survival (PFS) of ICB (I‐square value (I2) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09–1.49, I2 = 0.00%, OR 1.12, 95% CI 1.00–1.25, I2 = 42.1%, OR 0.81, 95% CI 0.72–0.92, I2 = 34.5%, OR 0.80, and 95% CI 0.71–0.89, respectively). Toxicity between combination therapy and ICB monotherapy did not significantly differ in any grade or in ≥3 grade of tr‐AEs (I2 = 0.00%, OR 1.05, 95% CI 0.91–1.22, I2 = 0.00%, OR 1.46, 95% CI 0.90–2.37, respectively). Subgroup analyses based on single‐arm studies showed that applications of SRS/SBRT, PD‐1 inhibitor, and administration of ICB after RT were conducive to a better DCR, longer OS and mild adverse events (heterogeneity between groups (HBG) all p

Abstract Diffuse large B cell lymphoma (DLBCL) expresses abundant programmed death ligand 1 (PD‐L1), which shields tumor cells from immune attacks through the PD‐L1/PD‐1 signaling axis. The mechanism of PD‐L1 overexpression includes the deletion of the 3′end of PD‐L1, which increases its mRNA stability, and the gain or amplification of PD‐L1. Previous studies found two cases of DLBCL carrying an IGH::PD‐L1 by whole genome sequencing. We describe two more such cases by a targeted DNA next‐generation sequencing (NGS) capable of detecting IGH rearrangements, leading to PD‐L1 overexpression. DLBCL with PD‐L1 overexpression is often resistant to R‐CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone). Our patients responded to a combination of R‐CHOP and a PD‐1 inhibitor.

Purpose: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning. Results: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28). Conclusions: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

Abstract Aging is always accompanied by chronic diseases which probably attribute to long‐term chronic inflammation in the aging body. Whereas, the mechanism of chronic inflammation in aging body is still obscure. Mesenchymal stem cells (MSCs) are capable of local chemotaxis to sites of inflammation and play a powerful role in immune regulation. Whether degeneration of MSCs in the aging body is associated with unbalanced inflammation is still not clear. In this study, immunosuppressive properties of aged MSCs are found to be repressed. The impaired immunosuppressive function of aged MSCs is associated with lower expression of the Hippo effector Yes‐associated protein 1 (YAP1) and its target gene signal transducer and activator of transcription 1 (STAT1). YAP1 regulates the transcription of STAT1 through binding with its promoter. In conclusion, a novel YAP1/STAT1 axis maintaining immunosuppressive function of MSCs is revealed and impairment of this signal pathway in aged MSCs probably resulted in higher inflammation in aged mice liver.

Cardiovascular diseases are the main killers threatening human health. Many studies have shown that abnormal energy metabolism plays a key role in the occurrence and development of acute and chronic cardiovascular diseases. Regulating cardiac energy metabolism is a frontier topic in the treatment of cardiovascular diseases. However, we are not very clear about the choice of different substrates, the specific mechanism of energy metabolism participating in the course of cardiovascular disease, and how to develop appropriate drugs to regulate energy metabolism to treat cardiovascular disease. Therefore, this paper reviews how energy metabolism participates in cardiovascular pathophysiological processes and potential drugs aimed at interfering energy metabolism.It is expected to provide good suggestions for promoting the clinical prevention and treatment of cardiovascular diseases from the perspective of energy metabolism.

Abstract Background The repair of white matter injury is of significant importance for functional recovery after ischemic stroke, and the up-regulation of triggering receptors expressed on myeloid cells 2 (TREM2) after ischemic stroke is neuroprotective and implicated in remyelination. However, the lack of effective therapies calls for the need to investigate the regenerative process of remyelination and the role of rehabilitation therapy. This study sought to investigate whether and how moderate physical exercise (PE) promotes oligodendrogenesis and remyelination in rats with transient middle cerebral artery occlusion (tMCAO). Methods Male Sprague–Dawley rats (weighing 250–280 g) were subjected to tMCAO. AAV-shRNA was injected into the lateral ventricle to silence the Trem2 gene before the operation. The rats in the physical exercise group started electric running cage training at 48 h after the operation. The Morris water maze and novel object recognition test were used to evaluate cognitive function. Luxol fast blue staining, diffusion tensor imaging, and electron microscopy were used to observe myelin injury and repair. Immunofluorescence staining was applied to observe the proliferation and differentiation of oligodendrocyte precursor cells (OPCs). Expression of key molecules were detected using immunofluorescence staining, quantitative real-time polymerase chain reaction, Western blotting, and Enzyme-linked immunosorbent assay, respectively. Results PE exerted neuroprotective efects by modulating microglial state, promoting remyelination and recovery of neurological function of rats over 35 d after stroke, while silencing Trem2 expression in rats suppressed the aforementioned effects promoted by PE. In addition, by leveraging the activin-A neutralizing antibody, we found a direct beneficial effect of PE on microglia-derived activin-A and its subsequent role on oligodendrocyte differentiation and remyelination mediated by the activin-A/Acvr axis. Conclusions The present study reveals a novel regenerative role of PE in white matter injury after stroke, which is mediated by upregulation of TREM2 and microglia-derived factor for oligodendrocytes regeneration. PE is an effective therapeutic approach for improving white matter integrity and alleviating neurological function deficits after ischemic stroke.

TRPV2 is activated by temperature and cannabinoids. Here, the authors have used cryo-EM and electrophysiology to identify a cannabinoid binding site distinct from that of cannabidiol as a possible drug target for treatment of inflammation and immune-mediated diseases.

Introduction: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. Methods: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. Results: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6–81) and 63 lesions (range: 6–126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1–10 fractions (20–70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3–91.9%). LC2 was 77.9% (95% CI: 66.4–86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0–51.4%) and PFS2 of 23.9% (95% CI: 17.8–31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2–85.0%) and OS2 of 60.7% (95% CI: 51.3–69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. Conclusions: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

A comprehensive understanding of rice straw (RS) and biochar (BC) addition affecting soil quality, enzyme activities, bacterial community structure and grain yield is crucial. The objective of this study was to examine the dynamics of the soil microbial community impacted by the application of rice straw and biochar, and to understand the relationship between the microbial communities, soil enzymes, nutrients and grain yield of paddies. We conducted a field experiment with organic amendments under the direct seeding of paddies. The bacterial community structure in the rhizosphere was characterized using high-throughput 16S rRNA sequencing. The results showed that RS amendment increased grain yields by 8.5 and 9.9% more than with BC and the control without organic amendment (CK), respectively (p < 0.05). The abundance of bacteria associated with nitrate reduction in RS was higher than that in BC and CK, which further showed the significance of the RS-treated soil bacteria in rice nutrient utilization. A cladogram plotted using linear discriminant analysis effect size showed that Proteobacteria (Alphaproteobacteria), Acidobacteria, Firmicutes, Verrucomicrobia and Epsilonbacteraeota in the RS-treated soil increased in comparison with CK. Pearson’s correlation analysis showed that enzymes activities (cellulase activity and protease activity), soil nutrition content (soil hydrolyzable nitrogen), and bacterial phyla (Nitrospinae) were positively correlated with grain yield, suggesting that the RS-treated soil improved enzyme activities, soil nutrition content, and bacterial abundance, which in turn increased grain yield. The results indicated that RS-treated bacterial communities combined with soil enzymatic activities strengthen the transformation of nutrients, suggesting that the interactions play an important role in enhancing the grain yield of paddy rice. These results provide new insights and a theoretical basis for studying the changes in soil microbial communities with the application of RS and BC in Northeastern China.

A new type of prefabricated foundation for onshore wind power was proposed in this paper. The stress and bearing mechanism of the new foundation was explored through theoretical calculation and finite element analysis. The results show that compared with the extended foundation in the same position, the amount of concrete in the new foundation is reduced by 30.00%, and the amount of rebars are reduced by 34.69%. The new prefabricated foundation has been inspected and calculated according to the specification. The calculation results indicate that the stress and initial reinforcement of the foundation meet the specification requirements. The bearing capacity, inclination rate, deformation, and stability of the foundation meet the requirements. Through finite element analysis, it is further confirmed that the structure meets the requirements of wind turbine operation, and the overall force meets the requirements of various indicators. The stress distribution of the foundation concrete and rebars is reasonable and uniform, and the load transfer is great. Also, the maximum stress of rebars and concrete does not exceed the specification limit, and the concrete remains intact without cracking or damage. The new foundation structural design and theoretical analysis were reasonable and accurate, and can be put into application in the future.

In recent years, graph neural networks (GNNs) have achieved great success in handling node classification tasks. However, as data explosively grows in various industries, the problem of class imbalance becomes increasingly severe. Traditional GNNs tend to prioritize majority class nodes when dealing with imbalanced class distributions, which fail to adequately capture the features of minority class nodes, leading to significant difficulties and challenges in data classification. To address issues such as inaccurate edge generation during graph data oversampling, insufficient representation of minority classes, and the presence of noisy samples, this paper proposes the ESA-GCN model. The advantages of this model are as follows: (i) it employs the ENN-SMOTE comprehensive sampling method to balance the dataset by reducing majority class nodes and increasing minority class nodes; (ii) the ENN algorithm reduces the classifier’s error rate and improves performance stability by removing low-quality and noisy data; (iii) an attention mechanism is introduced during the edge generation phase between new nodes and original nodes, fully considering the mutual relationships between nodes and concentrating on a subset of key information with high weights, thereby significantly improving classification accuracy while reducing model parameters and computational complexity. Experiments conducted on three public datasets (Cora, Citeseer, and PubMed) demonstrate that the ESA-GCN has achieved significant results in class imbalance node classification tasks.

ABSTRACT Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with the normal intestine, the pH value of the tumor microenvironment is weakly acidic. The metabolic changes of F. nucleatum in the tumor microenvironment, especially the protein composition of its outer membrane vesicles, remain unclear. Here, we systematically analyzed the effect of environmental pH on the proteome of outer membrane vesicles (OMVs) from F. nucleatum by tandem mass tag (TMT) labeling–high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of 991 proteins were identified in acidic OMVs (aOMVs) and neutral OMVs (nOMVs), including known virulence proteins and putative virulence proteins. Finally, 306 upregulated proteins and 360 downregulated proteins were detected in aOMVs, and approximately 70% of the expression of OMV proteins was altered under acidic conditions. A total of 29 autotransporters were identified in F. nucleatum OMVs, and 13 autotransporters were upregulated in aOMVs. Interestingly, three upregulated autotransporters (D5REI9, D5RD69, and D5RBW2) show homology to the known virulence factor Fap2, suggesting that they may be involved in various pathogenic pathways such as the pathway for binding with colorectal cancer cells. Moreover, we found that more than 70% of MORN2 domain-containing proteins may have toxic effects on host cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that a number of proteins were significantly enriched in multiple pathways involving fatty acid synthesis and butyrate synthesis. Seven metabolic enzymes involved in fatty acid metabolism pathways were identified in the proteomic data, of which 5 were upregulated and 2 were downregulated in aOMVs, while 14 metabolic enzymes involved in the butyric acid metabolic pathway were downregulated in aOMVs. In conclusion, we found a key difference in virulence proteins and pathways in the outer membrane vesicles of F. nucleatum between the tumor microenvironment pH and normal intestinal pH, which provides new clues for the prevention and treatment of colorectal cancer. IMPORTANCE F. nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. OMVs have been demonstrated to play key roles in pathogenesis by delivering toxins and other virulence factors to host cells. By employing quantitative proteomic analysis, we found that the pH conditions could affect the protein expression of the outer membrane vesicles of F. nucleatum. Under acidic conditions, approximately 70% of the expression of proteins in OMVs was altered. Several virulence factors, such as type 5a secreted autotransporter (T5aSSs) and membrane occupation and recognition nexus (MORN) domain-containing proteins, were upregulated under acidic conditions. A large number of proteins showed significant enrichments in multiple pathways involving fatty acid synthesis and butyrate synthesis. Proteomics analysis of the outer membrane vesicles secreted by pathogenic bacteria in the acidic tumor microenvironment is of great significance for elucidating the pathogenicity mechanism and its application in vaccine and drug delivery vehicles.

Frailty is a common geriatric syndrome characterized by increased vulnerability and is associated with adverse clinical events such as falls, hospitalization, and death. Early diagnosis and early intervention can delay or reverse frailty and ensure the healthy aging of older individuals. At present, there are no gold standard biomarkers for the diagnosis of frailty, which mainly relies on the scale to assess frailty, and the scale has shortcomings such as lagging assessment, subjectivity, and poor consistency. Frailty biomarkers help in early diagnosis and intervention in frailty. The purpose of this review is to summarize the existing inflammatory markers of frailty and focus on novel inflammatory biomarkers of frailty that can be used to help identify frailty early and explore potential intervention targets.

Background and purposeHPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV−) disease. We report a planned interim analysis of a prospective registry study that tailors chemoradiation (CRT) for anal cancer according to HPV status.Materials and methodsHPV+ patients received de-escalated radiation doses of 45, 50.4 and 55.8 Gy, while HPV− received 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively. Chemotherapy consisted of a single dose of mitomycin-C and oral capecitabine on days of RT. All patients were planned by VMAT following CT, PET/CT and MR simulation. This cohort (n = 24) had a minimum 24-month follow-up. Disease free survival (DFS) and local failure rates (LFR) were compared with 180 patients managed by standard CRT (2 cycles of mitomycin-C and 5-fluorouracil, radiation doses 50.4-63 Gy based on T-category) from 2011-2018. Propensity score comparison was performed using a retrospective to prospective 2 to 1 match based on tumor size and N-category.ResultsIn the HPV+ cohort (n = 20), there were 2 local failures. Two of 4 HPV− patients failed locally. The 30-month DFS and LFR were 79% and 17% respectively. Similar DFS and LFR were observed in the retrospective (80% and 15% respectively) and matched patients (76% and 16% respectively). No grade ≥3 neutropenia and febrile neutropenia were observed in the registry cohort whereas 19% and 14% respectively were seen in the retrospective patients.ConclusionDe-escalation of CRT for HPV+ anal cancer may result in decreased acute toxicities and similar cancer outcomes compared to standard CRT.

Abstract Background Grain length (GL) that is directly associated with appearance quality is a key target of selection in rice breeding. Although abundant quantitative trait locus (QTL) associated with GL have been identified, it was still relatively weak to identify QTL for GL from japonica genetic background, as the shortage of japonica germplasms with long grains. We performed QTLs analysis for GL using a recombinant inbred lines (RILs) population derived from the cross between japonica variety GY8 (short grains) and LX1 (long grains) in four environments. Results A total of 197 RILs were genotyped with 285 polymorphic SNP markers. Three QTLs qGL5.3, qGL6.1 and qGL11 were detected to control GL by individual environmental analyses and multi-environment joint analysis. Of these, a major-effect and stable QTL qGL6.1 was identified to be a novel QTL, and its LX1 allele had a positive effect on GL. For fine-mapping qGL6.1, a BC1F2 population consisting of 2,487 individuals was developed from a backcross between GY8 and R176, one line with long grain. Eight key informative recombinants were identified by nine kompetitive allele specific PCR (KASP) markers. By analyzing key recombinants, the qGL6.1 locus was narrowed down to a 40.41 kb genomic interval on chromosome 6. One candidate gene LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) was finally selected based on the difference in the transcriptional expression and variations in its upstream and downstream region. Conclusions Three QTLs qGL5.3, qGL6.1 and qGL11 were identified to control grain length in rice. One novel QTL qGL6.1 was fine mapped within 40.41 kb region, and LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) may be its candidate gene. We propose that the further cloning of the qGL6.1 will facilitate improving appearance quality in japonica varieties.

Abstract Background Isolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients. Methods We conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality. Results A total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan–Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count. Conclusions In hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Abstract Background Genetic testing (GT) for hereditary cancer predisposition is traditionally performed on selected genes based on established guidelines for each cancer type. Recently, expanded GT (eGT) using large hereditary cancer gene panels uncovered hereditary predisposition in a greater proportion of patients than previously anticipated. We sought to define the diagnostic yield of eGT and its clinical relevance in a broad cancer patient population over a 5-year period. Methods A total of 17,523 cancer patients with a broad range of solid tumors, who received eGT at Memorial Sloan Kettering Cancer Center between July 2015 to April 2020, were included in the study. The patients were unselected for current GT criteria such as cancer type, age of onset, and/or family history of disease. The diagnostic yield of eGT was determined for each cancer type. For 9187 patients with five common cancer types frequently interrogated for hereditary predisposition (breast, colorectal, ovarian, pancreatic, and prostate cancer), the rate of pathogenic/likely pathogenic (P/LP) variants in genes that have been associated with each cancer type was analyzed. The clinical implications of additional findings in genes not known to be associated with a patients’ cancer type were investigated. Results 16.7% of patients in a broad cancer cohort had P/LP variants in hereditary cancer predisposition genes identified by eGT. The diagnostic yield of eGT in patients with breast, colorectal, ovarian, pancreatic, and prostate cancer was 17.5%, 15.3%, 24.2%, 19.4%, and 15.9%, respectively. Additionally, 8% of the patients with five common cancers had P/LP variants in genes not known to be associated with the patient’s current cancer type, with 0.8% of them having such a variant that confers a high risk for another cancer type. Analysis of clinical and family histories revealed that 74% of patients with variants in genes not associated with their current cancer type but which conferred a high risk for another cancer did not meet the current GT criteria for the genes harboring these variants. One or more variants of uncertain significance were identified in 57% of the patients. Conclusions Compared to targeted testing approaches, eGT can increase the yield of detection of hereditary cancer predisposition in patients with a range of tumors, allowing opportunities for enhanced surveillance and intervention. The benefits of performing eGT should be weighed against the added number of VUSs identified with this approach.

Abstract Background Antibiotic-associated diarrhea (AAD) is diarrhea associated with consuming antibiotics that cannot be explained by other causes. AAD prolongs admission time and increases mortality and financial costs. Elderly individuals are more prone to receive antibiotic treatment and develop AAD. The finding that living probiotic microorganisms decrease AAD incidence in adults (

The relationship between parental genetic differences and the quality and yield of japonica hybrid rice strongly influences japonica hybrid rice breeding. In this study, 137 parental lines of japonica hybrid rice were genotyped using 8K rice SNP-Chips to characterize their genetic diversity, population structure, and indica-genotype proportion. The genetic diversity of total parental lines averaged 0.264, with values of 0.287 for restorer lines and 0.148 for the sterile lines. The introduction of indica lineage increased the genetic diversity of restorer lines relative to that of sterile lines. By model-based population structure analysis, the 137 lines were divided into 14 groups. According to the grouping results, eight restorer lines and five sterile lines were selected from different groups for cross breeding, yielding 40 japonica hybrid rice combinations (F1). Investigation of the yield and quality of these combinations showed that high-yield combinations could be obtained by increasing parental genetic distance to 0.8–0.9, a result accomplished largely by the introduction of indica genomic components of restorer lines. To further improve grain quality, the genetic distance between parents should be reduced to 0.4–0.5, suggesting an indica-genotype proportion of 30%–40% for restorer lines. This study may provide a reference for breeding of japonica hybrid rice.

A 22-year-old lady underwent penetrating keratoplasty for serious keratoconus. The following day, it was complicated by the development of infectious endophthalmitis. The source of infection was identified as carbapenem-resistant Klebsiella pneumoniae. The donor corneal button might be playing a role in infection transmission due to carbapenem-resistant Klebsiella pneumoniae in a sputum culture when the donor was still alive. Nosocomial infections were typically severe, rapidly progressive, and difficult to treat. Finally, the patient underwent therapeutic penetrating keratoplasty again with complete resolution of the infection.

BackgroundThere is insufficient evidence on the effect of Tai Chi Yunshou on improving balance and motor function in stroke survivors. Therefore, this systematic review and meta-analysis aimed to evaluate the effect of Tai Chi Yunshou on improving balance and motor function in stroke patients through a comprehensive literature search.MethodsEnglish and Chinese databases were searched from inception to February 10, 2023, to collect randomized controlled trials (RCTs) investigating the effects of Tai Chi Yunshou on balance and motor function in stroke survivors. Two reviewers independently selected studies meeting eligibility criteria, extracted required data, and assessed the risk of bias using methods recommended by the Cochrane Reviewers’ Handbook. Primary outcomes were balance function and motor function, while secondary outcomes included walking gait and activities of daily living. Review Manager software (version 5.4.1) was used for data analysis.ResultsAmong the 1,400 identified records, 12 eligible randomized controlled trials were finally included, with a total of 966 subjects. The results of the meta-analysis showed that the balance function of the experimental group and the control group was assessed using the Berg Balance Scale (MD = 4.87, p