Search

Abstract Background The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. Methods We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3 −/− and Cxcl10 −/− ) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3 −/− and Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3 −/− or Cxcl10 −/− recipient mice (CD45.2) and examined donor-contributed hematopoiesis. Results Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10 −/− donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. Conclusions The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.

Abstract Background The global public health issue of diminishing physical fitness among adolescents has gained increasing attention. The impact of parents’ negative emotions or pressure regarding adolescents’ educational aspirations may have a passive impact on the quality of life and adaptation of adolescents in and out of school, and ultimately harm their physical health. This study aims to explore whether parent-child discrepancies in educational aspirations influence physical fitness in adolescents through school adaptation and quality of life. Methods Participants consisted of 9,768 students, males 4,753(48.7%), females 5,015(51.3%), aged 11–19 years, males 14.3 ± 1.92, females 14.4 ± 1.93. The educational aspirations were gauged using a six-point scale for expectation scores. Physical fitness assessments were based on criteria from the National Student Physical Fitness and Health Survey. School adaptation was evaluated using the School Social Behaviors Scale-2. Quality of life for adolescents was measured using Chinese version of the Quality of Life Scale for Children and Adolescents. To analyze the multiple mediating effects, structural equation models were used, and 95% confidence intervals were determined through bootstrap methods. Results The results illustrated that school adaptation and quality of life played a significant mediating role in the effect of parent-child discrepancies in educational aspirations and physical fitness. There were three intermediary paths were confirmed: (1) discrepancies in educational aspirations → school adaptation → physical fitness (β=-0.088 SE = 0.021; p

Quantum secure direct communication (QSDC) can directly transmit secret messages through quantum channel without keys. Device-independent (DI) QSDC guarantees the message security relying only on the observation of the Bell-inequality violation, but not on any detailed description or trust of the devices’ inner workings. Compared with conventional QSDC, DI-QSDC has relatively low secret message capacity. To increase DI-QSDC’s secret messages capacity, we propose a high-capacity DI-QSDC protocol based on the hyper-encoding technique. The total message leakage rate of our DI-QSDC protocol only relies on the most robust degree of freedom. We provide the numerical simulation of its secret message capacity altered with the communication distance. Our work serves as an important step toward the further development of DI-QSDC systems.

Abstract Background Insulin resistance (IR) and arthritis are strongly associated, and the triglyceride–glucose (TyG) index combinations with obesity indicators [including TyG–BMI (glucose triglyceride–body mass index), TyG–WC (glucose triglyceride–waist circumference), and TyG–WHtR (glucose triglyceride–waist height ratio)] has recently been recognized as a more effective indicator for assessing IR. However, there is a lack of research on its association with arthritis, and it is also important to assess in different populations. Methods The analysis utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). Arthritis diagnosis relied on self-reporting confirmed by physicians. The association of TyG–BMI, TyG–WC, and TyG–WHtR with arthritis was analyzed through weighted logistic regression models, and exploring nonlinear effects with restricted cubic spline (RCS) models. Secondary and sensitivity analyses included receiver operating characteristic curve (ROC) analysis, comparisons of z score-related odds ratios, subgroup analyses, and multiple imputation. Results The study involved 6141 CHARLS participants and 17,091 NHANES participants. Adjusting for confounding variables, TyG–BMI and TyG–WHtR demonstrate a positive correlation with arthritis prevalence in both CHARLS (TyG–BMI: OR = 1.02, 95% CI 1.00–1.04; TyG–WHtR: OR = 1.13, 95% CI 1.03–1.24) and NHANES (TyG–BMI: OR = 1.07, 95% CI 1.06–1.08; TyG–WHtR: OR = 1.50, 95% CI 1.40–1.60). RCS regression analysis demonstrated a significant nonlinear association. ROC analysis indicated that TyG–BMI and TyG–WHtR were superior to TyG for the diagnosis of arthritis in both CHARLS and NHANES. Conclusions TyG–BMI and TyG–WHtR demonstrate a positive correlation with arthritis prevalence in both Chinese and the U.S. populations, displaying superior diagnostic relevance compared to TyG.

Background: Numerous approaches have been utilized to optimize mesenchymal stem cells (MSCs) performance in treating osteoarthritis (OA), however, the constrained diminished activity and chondrogenic differentiation capacity impede their therapeutic efficacy. Previous investigations have successfully shown that pretreatment with nanosecond pulsed electric fields (nsPEFs) significantly enhances the chondrogenic differentiation of MSCs. Therefore, this study aims to explore nsPEFs as a strategy to improve OA therapy by enhancing MSCs' activity and chondrogenic differentiation and also investigate its potential mechanism. Methods: In this study, a million MSCs were carefully suspended within a 0.4-cm gap cuvette and subjected to five pulses of nsPEFs (100 ns at 10 kV/cm, 1 Hz), with a 1-s interval between each pulse. A control group of MSCs was maintained without nsPEFs treatment for comparative analysis. nsPEFs were applied to regulate the MSCs performance and hinder OA progresses. In order to further explore the corresponding mechanism, we examined the changes of MSCs transcriptome after nsPEF pretreatment. Finally, we studied the properties of extracellular vesicles (EVs) secreted by MSCs affected by nsPEF and the therapeutic effect on OA. Results: We found that nsPEFs pretreatment promoted MSCs migration and viability, particularly enhancing their viability temporarily in vivo, which is also confirmed by mRNA sequencing analysis. It also significantly inhibited the development of OA-like chondrocytes in vitro and prevented OA progression in rat models. Additionally, we discovered that nsPEFs pretreatment reprogrammed MSC performance by enhancing EVs production (5.77 ± 0.92 folds), and consequently optimizing their therapeutic potential. Conclusions: In conclusion, nsPEFs pretreatment provides a simple and effective strategy for improving the MSCs performance and the therapeutic effects of MSCs for OA. EVs-nsPEFs may serve as a potent therapeutic material for OA and hold promise for future clinical applications. The translational potential of this article: This study indicates that MSCs pretreated by nsPEFs greatly inhibited the development of OA. nsPEFs pretreatment will be a promising and effective method to optimize the therapeutic effect of MSCs in the future.

Abstract Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications. Graphical Abstract

Abstract Background Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing. Objective The aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants. Methods Patients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members. Results A three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance. Conclusion This study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.

Background: The fingertip amputation is an amputation type of the finger beyond the proximal nail fold. There is no vein available for anastomoses on the dorsal side of the finger, and the palmar vein of the finger is small and tightly attached to the skin. Therefore, it is relatively difficult to implement surgical anastomoses, which poses challenges to the clinical treatment of fingertip amputations. Case report: A 29-year-old male was admitted to the hospital due to “the amputation of the fingertips of the right index, middle, and ring fingers caused by a heavy object compression 3 h ago”. The admission examination revealed that the right index, middle, and ring fingers were completely severed at the 1/2 plane of the nail bed, with irregular sections, severe contusion, and pollution. The X-ray examination showed comminuted fractures of the distal phalanges of the right index, middle, and ring fingers. Based on these findings, the patient was diagnosed with multiple severed fingertips of the right hand (Tamai Zone 1). The patient underwent debridement, vascular exploration, and replantation of the right index, middle, and ring fingertips under emergency general anesthesia. After surgery, anti-inflammatory, spasmolytic, and anticoagulant treatment and regular dressing changes were conducted. The patient did not receive a blood transfusion, and all three fingers survived. The appearance of these fingers was favorable 3 months after surgery, and the flexion and extension of these fingers were normal. Eventually, the patient achieved excellent Chen's hand function scores. Conclusions: To the best of our knowledge, this may be the first successful case regarding the replantation of three fingertips after amputations in Tamai Zone 1 with favorable outcomes. It can be maintained that super microsurgery can be used for the replantation of multiple fingertip amputations.

Background: As a chronic inflammatory process, chronic osteomyelitis is caused by bacterial infections that lead to bone destruction. This disease is more common in patients with open fractures and those undergoing multiple surgical procedures after trauma. We aimed to provide a comprehensive overview and critical assessment of the therapeutic efficacy of the anterolateral thigh (ALT) perforator flap in the management of chronic osteomyelitis with dermatologic and soft tissue imperfections localized in the lower extremity. Methods: A retrospective analysis involving a cohort of 16 patients who underwent ALT perforator flap reconstruction for the management of chronic osteomyelitis in the calf region that manifested with integumentary deficiencies was conducted. Results: During the follow-up period spanning from 4 months to 2 years, all 16 patients who underwent ALT perforator flap transplantation exhibited flap viability. Among these cases, 15 patients made a full recovery from the infection and 1 patient had partial survival. Among the 15 cases, 2 patients developed vascular crisis (owing to venous thrombosis during surgical exploration). One patient had a relapse of the disease 1-year post-surgery. The success rate of this surgical method was 15/16, and the surgical complications included flap crisis, flap necrosis, delayed wound healing, and recurrence of infection. Conclusion: The ALT perforator flap, which can cover bone and soft tissues and effectively control infections, can be applied to the treatment of chronic osteomyelitis of the lower limbs with skin defects. Overall, the muscle flap fills the dead space and medullary cavity and skin flap covers the skin defect.

Abstract Background A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. Methods The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. Results The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P

Abstract Bacterial ClpB is an ATP-dependent disaggregate that belongs to the Hsp100/Clp family and facilitates bacterial survival under hostile environmental conditions. Streptococcus agalactiae, which is regarded as the major bacterial pathogen of farmed Nile tilapia (Oreochromis niloticus), is known to cause high mortality and large economic losses. Here, we report a ClpB homologue of S. agalactiae and explore its functionality. S. agalactiae with a clpB deletion mutant (∆clpB) exhibited defective tolerance against heat and acidic stress, without affecting growth or morphology under optimal conditions. Moreover, the ΔclpB mutant exhibited reduced intracellular survival in RAW264.7 cells, diminished adherence to the brain cells of tilapia, increased sensitivity to leukocytes from the head kidney of tilapia and whole blood killing, and reduced mortality and bacterial loads in a tilapia infection assay. Furthermore, the reduced virulence of the ∆clpB mutant was investigated by transcriptome analysis, which revealed that deletion of clpB altered the expression levels of multiple genes that contribute to the stress response as well as certain metabolic pathways. Collectively, our findings demonstrated that ClpB, a molecular chaperone, plays critical roles in heat and acid stress resistance and virulence in S. agalactiae. This finding provides an enhanced understanding of the functionality of this ClpB homologue in gram-positive bacteria and the survival strategy of S. agalactiae against immune clearance during infection.

Abstract Background Microbial communities are crucial for ecosystems. A central goal of microbial ecological research is to simplify the biodiversity in natural environments and quantify the functional roles to explore how the ecosystems respond under different environmental conditions. However, the research on the stability and dynamics of lake microbes in response to repeated warming stress is limited. Methods To exclude confounding environmental factors, we conducted a 20-day repeated warming simulation experiment to examine the composition and function dynamics of lake microbial communities. Results Experimental warming significantly altered the community structure of bacteria instead of fungi. Microbial community structure, together with microbial biomass, jointly regulated the function of microbial communities. The plummeting of aerobic denitrifiers Pseudomonadaceae decreased by 99% (P

Abstract Object detection in remote sensing images poses great challenges due to the dense distribution, arbitrary orientation, and aspect ratio variations of objects. Most of the existing methods rely on aligned convolutional features, which fail to capture the geometric information of objects effectively and result in the inconsistency between the classification score and localization accuracy. Moreover, densely packed objects suffer from spatial feature aliasing caused by the intersection of reception fields between objects. To address this issue, a deformable convolution‐based method named rotated points is proposed, which consists of two modules: a point set loss module and a high‐quality sample assignment module. The point set loss module can extract geometric features of objects in arbitrary directions with fine‐grained point sets for feature representation and introduce outlier penalties to penalize outlier points. The high‐quality sample assignment module measures the classification and localization ability, orientation quality, and point‐wise correlation of point sets comprehensively to enhance the consistency of classification and regression significantly. Experiments on the DOTA and FAIR1M datasets demonstrate that the proposed method achieves significant improvements over the benchmark model.

The first occurrence of Marasmiellomycena and Pulverulina in the Chinese mycobiota are reported, M. tomentosa and P. flavoalba, two new species and M. albodescendens, a new combination, revealed by phylogenetic analyses and morphological study. These newly-recorded genera, Marasmiellomycena, which can be distinguished by their agaricoid basidiomata, dark-coloured stipe, sarcodimitic tramal structure, stipitipellis with yellow to yellowish-brown pigments and yellow-pigmented thick-walled caulocystidia and Pulverulina, which differs from other genera of Porotheleaceae by its pruinose stipe, decurrent lamellae, inamyloid basidiospores and absence of hymenial cystidia. We also formally describe three other new species of Porotheleaceae collected from Chinese temperate to subtropical zones of Fujian and Zhejiang Provinces: Clitocybula fuscostriata, Gerronema brunneosquamulosum and Leucoinocybe subglobispora. Furthermore, we include the results of a phylogenetic analysis of Porotheleaceae, based on a multi-locus (ITS, nrLSU and rpb2) dataset. According to this analysis, Chrysomycena, Clitocybula, Delicatula, Hydropodia, Hydropus, Leucoinocybe, Marasmiellomycena, Megacollybia, Pulverulina, Trogia and Vizzinia are monophyletic. However, Gerronema is identified as polyphyletic and, additionally, Porotheleum does not form a monophyletic group either because Porotheleum parvulum and Porotheleum albidum are “unassigned” in phylogenetic analysis. The results of our phylogenetic analyses, coupled with morphological observations, confirm recognition of these new taxa. Morphological descriptions, photographs, line drawings and comparisons with closely-related taxa are presented for the new species. A key to the 22 species belonging to nine genera of Porotheleaceae in China is also provided.

Abstract Background The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). Methods 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. Results Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P

Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.

Summary:. A 50-year-old man was admitted to the hospital with a chief complaint of long-standing cold-induced numbness in the fingers for more than a year, accompanied by persistent hand pain and fingertip ulceration for 3 months. On physical examination, radial and ulnar artery pulsation was absent in both limbs, and pale skin color, low skin temperature, and limited finger range of motion were noted. Gangrene was detected in the fingertips of the left index and middle fingers, and the right middle and ring fingers. The patient was diagnosed with bilateral arterial occlusion and vibration white finger. Upon admission, the patient underwent an intervention surgery on the right side. Subsequently, transplantation of the descending branches of the left and right lateral femoral circumflex arteries was performed to restore blood flow in the bilateral radial arteries. Additionally, debridement was conducted without shortening after the surgical procedure, the patient received anticoagulation, anti-inflammatory, and symptomatic treatment. The bilateral finger skin temperature increased by 3 °C postoperatively, and the accompanying pain and numbness were alleviated. The wound healed 1 month after surgery, and no recurrence of pain or ulcer was reported during the 1-year follow-up period. Eventually, his hand function recovered, without any impact on the vascular donor site.

Over the last decade, significant advancements have been made in breast-conserving surgery (BCS) for breast cancer. However, there is a lack of analytical and descriptive investigations on the trajectory, essential research directions, current research scenario, pivotal investigative focuses, and forthcoming perspectives. The objective of this research is to provide a thorough update on the progress made in BCS for breast cancer over the preceding decade. Retrieved from the Web of Science database, the data span from January 1, 2013, to November 30, 2023. Utilizing a set of advanced analytical instruments, we conducted comprehensive bibliometric and visual analyses. The findings underscore the predominant influence of the USA, representing 35.77% of the overall publications and playing a pivotal role in shaping research within this field. Notable productivity was evident at various institutions, including the Memorial Sloan Kettering Cancer Center, the University of Texas MD Anderson Cancer Center, and the University of Toronto. Annals of Surgical Oncology contributed the most publications in this field. An examination of keywords indicated a change in the concentration of research attention, transitioning from molecular subtype, ultrasonography, and intraoperative aspects to SEER, male breast cancer, and adjuvant measures. By offering a comprehensive bibliometric assessment, this study enhances our understanding of BCS for breast cancer. Consequently, this benefits both experienced researchers and newcomers alike, providing prompt access to essential information and fostering the extraction of innovative concepts within this specific field.

Osteoarthritis (OA) is a degenerative disease linked to aging and obesity. The global aging population has led to an increasing number of OA patients, imposing a significant economic burden on society. Traditional drugs treatment methods often fail to achieve satisfactory outcomes. With the rapid advancement of nanomaterial delivery systems, numerous studies have focused on utilizing nanomaterials as carriers to achieve efficient OA treatment by effectively loading and delivering bioactive ingredients (e.g., drugs, nucleic acids) tailored to the unique pathological conditions, such as the weakly acidic microenvironment of synovial fluid in OA patients. This review highlights the latest advancements in the use of pH-responsive nanoparticles for OA treatment, emphasizing the principle of targeted drug delivery leveraging the acidic microenvironment of inflamed joints. It further discusses the composition, synthesis, response mechanism, target selection, application, and recent research findings of nanoparticles, while also addressing the challenges and future directions in this promising field.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1β-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

Summary: Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Osteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive. Methods Hub genes were screened by bioinformatics analysis based on the GSE114007 and GSE169077 datasets. The Sprague–Dawley (SD) rat model of OA was constructed by intra-articular injection of a mixture of papain and L-cysteine. Hematoxylin–eosin (HE) staining was used to detect pathological changes in OA rat models. Inflammatory cytokine levels in serum were measured employing the enzyme-linked immunosorbent assay (ELISA). The reverse transcription quantitative PCR (RT-qPCR) was implemented to assess the hub gene expressions in OA rat models. The roles of PDK4 and the mechanism regulating the PPAR pathway were evaluated through western blot, cell counting kit-8 (CCK-8), ELISA, and flow cytometry assays in C28/I2 chondrocytes induced by IL-1β. Results Six hub genes were identified, of which COL1A1, POSTN, FAP, and CDH11 expressions were elevated, while PDK4 and ANGPTL4 were reduced in OA. Overexpression of PDK4 inhibited apoptosis, inflammatory cytokine levels (TNF-α, IL-8, and IL-6), and extracellular matrix (ECM) degradation protein expressions (MMP-3, MMP-13, and ADAMTS-4) in IL-1β-induced chondrocytes. Further investigation revealed that PDK4 promoted the expression of PPAR signaling pathway-related proteins: PPARA, PPARD, and ACSL1. Additionally, GW9662, an inhibitor of the PPAR pathway, significantly counteracted the inhibitory effect of PDK4 overexpression on IL-1β-induced chondrocytes. Conclusion PDK4 inhibits OA development by activating the PPAR pathway, which provides new insights into the OA management.

Abstract As satellite imagery technology advances, remote sensing plays an increasingly prominent role in modern society. Nevertheless, the limitations of existing imaging sensors and complex atmospheric conditions constrain the quality of raw remote sensing data, posing challenges for interpretation and noise reduction. Super‐resolution technology focuses on enhancing low‐quality, low‐resolution remote sensing images. In this study, we introduce a method that utilizes a high‐order degradation model to generate low‐resolution remote sensing images. We employ a Generative Adversarial Network with a Convolutional Block Attention Module (CBAM‐GAN) to enhance these images, reducing noise interference and improving texture and feature display. Our approach outperforms other methods on the UCMerced‐LandUse, WHU‐RS19, and AID datasets. Specifically, it raises SSIM index scores to 0.9443, 0.8928, and 0.8633, respectively, exceeding baselines by 1.31%, 0.19%, and 1.30%. The MOS index also improves to 3.98, 3.96, and 3.83, respectively, representing a 2.31%, 8.20%, and 2.96% gain over the baseline. Our reconstruction produces superior results, demonstrating the effectiveness of our proposed method.

Frequency spatial distribution characteristics of interconnected power systems are highlighted, resulting in significant regional frequency differences and inter-region tie-line power fluctuations, posing a threat to frequency security operation. For two-region interconnected power systems, analytical expressions for regional frequency and inter-regional tie-line power are derived based on the low-order frequency response model. By dividing the fast-varying part and the slow-varying part of the above analytical expressions, analytical frequency security indicators including nadir value, quasi-steady-state value, maximum rate value of regional frequency, and peak value, quasi-steady-state value of inter-regional tie-line power are derived. By dividing the fast-varying part and slow-varying part of the aforementioned analytical expressions, we further derived analytical frequency security indicators, including nadir value, quasi-steady-state value, maximum rate value of regional frequency, and peak value, quasi-steady-state value of inter-area tie-line power. Through case studies based on the IEEE 2-region 4-machine system, the results indicate that the obtained analytical frequency security indicators can accurately describe the frequency dynamics following a major disturbance for two-region interconnected power systems.

In response to the challenge of accurately assessing age-friendly design requirements during the improvement phase of smart products, a novel evaluation model is proposed. This model is grounded in the technology acceptance model and considers the interplay between user weights and requirements. The aim is to establish precise product indicators and development strategies, thereby maximizing user satisfaction and market competitiveness. Initially, design evaluation indicators are derived from the technology acceptance model. Subsequently, the TextRank algorithm and grounded theory are employed to determine the initial weights of these indicators. The DEMATEL method is utilized to analyze the weight of influence relationships between indicators, while the Kano model determines importance coefficients for adjusting weights. Through normalization, final weights are assigned, and the TOPSIS method implements sorting and significance analysis of age-friendly design requirements. Five age-friendly smartphone samples serve as case studies to evaluate and analyze the five age-friendly design requirement indicators. Method comparison and advantage/disadvantage sorting analyses are conducted to validate the effectiveness and feasibility of the proposed approach.

Abstract Background The cancer-immunity cycle (CI cycle) provides a theoretical framework to illustrate the process of the anticancer immune response. Recently, the update of the CI cycle theory emphasizes the importance of tumor’s immunological phenotype. However, there is lack of immunological phenotype of pan-cancer based on CI cycle theory. Methods Here, we applied a visualizing method termed ‘cancer immunogram’ to visualize the state of CI cycle of 8460 solid tumors from TCGA cohort. Unsupervised clustering of the cancer immunogram was performed using the nonnegative matrix factorization (NMF) analysis. We applied an evolutionary genomics approach (dN/dS ratio) to evaluate the clonal selection patterns of tumors with distinct immunogram subtypes. Results We defined four major CI cycle patterns across 32 cancer types using a cancer immunogram approach. Immunogram-I was characterized by ‘hot’ and ‘exhausted’ features, indicating a favorable prognosis. Strikingly, immunogram-II, immunogram-III, and immunogram-IV represented distinct immunosuppressive patterns of ‘cold’ tumor. Immunogram-II was characterized by ‘cold’ and ‘radical’ features, which represented increased expression of immune inhibitor molecules and high levels of positive selection, indicating the worst prognosis. Immunogram-III was characterized by ‘cold’ and ‘recognizable’ features and upregulated expression of MHC I molecules. Immunogram-IV was characterized by ‘cold’ and ‘inert’ features, which represented overall immunosuppression, lower levels of immunoediting and positive selection, and accumulation of more tumor neoantigens. In particular, favorable overall survival was observed in metastatic urothelial cancer patients with immunogram-I and immunogram-IV after immune checkpoint inhibitor (ICI) therapy. Meanwhile, a higher response rate to ICI therapy was observed in metastatic gastric cancer patients with immunogram-I phenotype. Conclusions Our findings provide new insight into the interaction between immunity and cancer evolution, which may contribute to optimizing immunotherapy strategies.

Summary: Ferroptosis is implicated in several diseases, including iron overload-induced osteoarthritis (IOOA), which is marked by oxidative stress, iron imbalance, and lipid peroxidation. Given rosiglitazone’s (RSG) ability to inhibit lipid peroxidation and ferroptosis, this study aims to assess its therapeutic potential for treating IOOA. Our in vitro results show that RSG targets acyl-CoA synthetase long-chain family member 4 to mitigate impairments induced by interleukin-1 beta and ferric ammonium citrate, including cell apoptosis, senescence, inflammatory responses, extracellular matrix degradation, and ferroptosis. RSG reduced intracellular iron content, alleviated oxidative stress and lipid peroxidation, mitigated damage to membrane-bound organelles, and enhanced glucose transport. Additionally, pre-treatment with RSG imparted anti-ferroptotic properties to chondrocytes. In vivo, RSG alleviated cartilage degradation, inflammatory responses, and ferroptosis in mice with IOOA. In conclusion, RSG exhibits chondroprotective and anti-ferroptotic effects by suppressing lipid peroxidation and restoring iron homeostasis, highlighting its potential for treating IOOA.

Aims: Despite its implication in various human cancers, the expression and functional significance of Kinesin family member 15 (KIF15) in chordomas remain unexplored. Main methods: The evaluation of KIF15 protein levels was conducted through immunohistochemistry (IHC) staining and Western blot analysis. Cell proliferation was quantified using MTT and CCK8 assays, whereas cell migration was examined using wound healing and Transwell assays. Furthermore, flow cytometric analysis was utilized to assess cell apoptosis and the cell cycle. Additionally, in vivo experiments were performed using a mouse xenograft model. Key findings: Our study revealed significantly higher expression of KIF15 in stage III chordoma tissues compared to stage II tissues. Knockdown of KIF15 led to notable inhibition of cell proliferation and migration, along with enhanced apoptosis and cell cycle arrest. In vivo studies further confirmed the inhibitory effects of KIF15 knockdown on chordoma tumour growth. In terms of mechanism, we identified the involvement of the PI3K-AKT signalling pathway mediated by KIF15 in chordomas. Notably, the anti-tumour effects of KIF15 deficiency on chordomas were partially reversed by the addition of an AKT activator. Significance: KIF15 promotes chordoma development and progression through the activation of the PI3K-AKT signalling pathway. Thus, targeting KIF15 might be a promising therapeutic strategy for treating chordomas.

Degenerative orthopaedic diseases pose a notable worldwide public health issue attributable to the global aging population. Conventional medical approaches, encompassing physical therapy, pharmaceutical interventions, and surgical methods, face obstacles in halting or reversing the degenerative process. In recent times, exosome-based therapy has gained widespread acceptance and popularity as an effective treatment for degenerative orthopaedic diseases. This therapeutic approach holds the potential for “cell-free” tissue regeneration. Exosomes, membranous vesicles resulting from the fusion of intracellular multivesicles with the cell membrane, are released into the extracellular matrix. Addressing challenges such as the rapid elimination of natural exosomes in vivo and the limitation of drug concentration can be effectively achieved through various strategies, including engineering modification, gene overexpression modification, and biomaterial binding. This review provides a concise overview of the source, classification, and preparation methods of exosomes, followed by an in-depth analysis of their functions and potential applications. Furthermore, the review explores various strategies for utilizing exosomes in the treatment of degenerative orthopaedic diseases, encompassing engineering modification, gene overexpression, and biomaterial binding. The primary objective is to provide a fresh viewpoint on the utilization of exosomes in addressing bone degenerative conditions and to support the practical application of exosomes in the theranosis of degenerative orthopaedic diseases.

Background: Liver cancer has a high incidence and mortality rate worldwide, and there is an urgent need to identify new therapeutic strategies and predictive targets to improve the clinical outcomes of advanced liver cancer. Ferroptosis holds promise as a novel strategy for cancer therapy. Epigenetic dysregulation is a hallmark of cancer, and noncoding RNAs are tightly involved in cell fate determination. Therefore, we aimed to identify a novel ferroptosis regulator from aberrantly expressed microRNAs that may serve as a novel biomarker and therapeutic target for liver cancer. Methods: The expression signature and prognostic value of miR-339 was assessed using TCGA data set. The role of miR-339/ATG7/FTH1 axis in liver cancer cells were evaluated through growth curve, colony formation, 7-AAD staining. The role of miR-339 in regulation of ferroptosis was determined by immunofluorescence staining, flow cytometry, and Elisa kits. Results: Here, we showed that miR-339 is aberrantly overexpressed in patients with liver cancer. In addition, miR-339 inhibition dramatically suppresses liver cancer progression. Furthermore, miR-339 silencing drives cell death and inhibits liver cancer progression, indicating that miR-339 may serve as a novel ferroptosis suppressor. Mechanistically, we demonstrated that miR-339 targets ATG7 to facilitate the autophagic degradation of FTH1 and prevent ferroptosis in liver cancer cells. Conclusions: We provide important evidence that the miR-339 inhibition activates of the autophagy pathway to promote ferroptosis by degrading FTH1 in liver cancer cells. We found that miR-339 regulates the balance between ferroptosis and autophagy in liver cancer cells.

ABSTRACTHorizontal gene transfer (HGT) is the process through which genetic information is transferred between different genomes and that played a crucial role in bacterial evolution. HGT can enable bacteria to rapidly acquire antibiotic resistance and bacteria that have acquired resistance is spreading within the microbiome. Conventional methods of characterizing HGT patterns include short-read metagenomic sequencing (short-reads mNGS), long-read sequencing, and single-cell sequencing. These approaches present several limitations, such as short-read fragments, high amounts of input DNA, and sequencing costs, respectively. Here, we attempt to circumvent present limitations to detect HGT by developing a metagenomics co-barcode sequencing workflow (MECOS) and applying it to the human and mouse gut microbiomes. In addition to that, we have over 10-fold increased contig length compared to short-reads mNGS; we also obtained exceeding 30 million paired reads with co-barcode information. Applying the novel bioinformatic pipeline, we integrated this co-barcoding information and the context information from long reads, and observed over 50-fold HGT events after we corrected the potential wrong HGT events. Specifically, we detected approximately 3,000 HGT blocks in individual samples, encompassing ~6,000 genes and ~100 taxonomic groups, including loci conferring tetracycline resistance through ribosomal protection. MECOS provides a valuable tool for investigating HGT and advance our understanding on the evolution of natural microbial communities within hosts.IMPORTANCEIn this study, to better identify horizontal gene transfer (HGT) in individual samples, we introduce a new co-barcoding sequencing system called metagenomics co-barcoding sequencing (MECOS), which has three significant improvements: (i) long DNA fragment extraction, (ii) a special transposome insertion, (iii) hybridization of DNA to barcode beads, and (4) an integrated bioinformatic pipeline. Using our approach, we have over 10-fold increased contig length compared to short-reads mNGS, and observed over 50-fold HGT events after we corrected the potential wrong HGT events. Our results indicate the presence of approximately 3,000 HGT blocks, involving roughly 6,000 genes and 100 taxonomic groups in individual samples. Notably, these HGT events are predominantly enriched in genes that confer tetracycline resistance via ribosomal protection. MECOS is a useful tool for investigating HGT and the evolution of natural microbial communities within hosts, thereby advancing our understanding of microbial ecology and evolution.

We study the holographic s+p model in both four dimensional (4D) and five dimensional (5D) Einstein-Gauss-Bonnet (EGB) gravity. We first show a phase diagram with the Gauss-Bonnet parameter fixed to a small value α=10−7 to choose appropriate values of qp/qs. Then we fix the value of qp/qs and plot α−μ phase diagrams to show the influence of Gauss-Bonnet term on the phase transitions in both 4D and 5D bulk, respectively. The phase diagrams in 4D and 5D present the same qualitative features, indicating similarity of 4D Einstein-Gauss-Bonnet gravity with the 5D case in holography. We also study the influences of the Gauss-Bonnet parameter on the special values of the fourth order nonlinear term parameters λs and λp, below which the condensate grows to a different direction near the critical point, that is important in realizing 1st order superfluid phase transitions. Especially, we notice that these special values are different in the canonical and grand canonical ensembles, which is closely related to the study of the spinodal region, where the phase separations occur with the linear instability at finite wave vector.

Abstract Background Venetoclax is clinically active in treating relapsed/refractory multiple myeloma (RRMM). This study evaluated the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Methods PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched. We included studies investigating the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Overall response rates (ORR), stringent complete response rates (sCR), complete response rates (CR), very good partial response rates (VGPR), partial response rates (PR), stable disease (SD), progressive disease (PD) and adverse events were synthesized using either a random-effects model or a fixed-effects model. Results A total of 7 clinical trials with 482 patients with RRMM were included. Concerning venetoclax with other agents, the pooled ORR, sCR, CR, VGPR, PR, SD, and PD were 0.76 (95% CIs: 0.62, 0.87), 0.11 (95% CIs: 0.04, 0.21), 0.18 (95% CIs: 0.11, 0.26), 0.16 (95% CIs: 0.12, 0.25), 0.29 (95% CIs: 0.25, 0.34), 0.07 (95% CIs: 0.05, 0.10), and 0.11 (95% CIs: 0.04, 0.23). The overall rate of adverse events ≥ Grade 3 was 0.84 (95% CIs: 0.77, 0.91). The most common non-hematologic adverse events were nausea, diarrhea, fatigue, back pain, and vomiting; hematologic adverse events included thrombocytopenia, neutropenia, anemia, leukopenia, and lymphopenia. Conclusions This study indicates that venetoclax alone or in combination with other agents reveals favorable treatment responses and acceptable adverse events in treating RRMM.

Abstract Background This study aimed to establish a nomogram for predicting risk of recurrence and provide a model for decision‐making between lobectomy and sublobar resection in patients with stage IA lung adenocarcinoma. Methods Patients diagnosed with stage IA lung adenocarcinoma (LUAD) between December 2010 and October 2018 from Cancer Hospital Chinese Academy of Medical Sciences were included. Patients were randomly assigned to training and validation cohorts, accounting for 70% and 30% of the total cases, respectively. We collected laboratory variables before surgery. Univariate and multivariate analyses were performed in the training cohort to identify variables significantly associated with recurrence‐free survival (RFS) which were subsequently used to construct a nomogram. Validation was conducted in both cohorts. A receiver operating characteristic curve was used to determine the optional cutoff values of the scores calculated from the nomogram. Patients were then divided into low‐ and high‐risk groups. Survival was performed to determine if the nomogram could guide the operation method. Results A total of 543 patients were included in this study. Gender, albumin level, carcinoembryonic antigen level and cytokeratin‐19‐fragment level were included in the nomogram. In both cohorts, the nomogram stratified the patients into high‐ and low‐risk groups in terms of RFS. In particular, there was a significant difference in RFS between lobectomy and sublobar resection in the high‐risk group. Conclusions Gender, albumin level, carcinoembryonic antigen level and cytokeratin‐19‐fragment level are valuable markers in predicting recurrence and can guide surgical practice in patients with stage IA LUAD.

Abstract Background Cell division cycle 6 (CDC6) is a key licensing factor in the assembly of pre-replicative complexes at origins of replication. The role of CDC6 in the pathogenesis of in diffuse larger B-cell lymphoma (DLBCL) remains unknown. We aim to investigate the effects of CDC6 on the proliferation, apoptosis and cell cycle regulation in DLBCL cells, delineate its underlying mechanism, and to correlate CDC6 expression with clinical characteristics and prognosis of patients with DLBCL. Methods Initial bioinformatic analysis was performed to screen the potential role of CDC6 in DLBCL. Lentiviral constructs harboring CDC6 or shCDC6 was transfected to overexpress or knockdown CDC6 in SUDHL4 and OCI-LY7 cells. The cell proliferation was evaluated by CCK-8 assay, cell apoptosis was detected by Annexin-V APC/7-AAD double staining, and cell cycle was measured by flow cytometry. Real time quantitative PCR and western blot was used to characterize CDC6 expression and its downstream signaling pathways. The clinical data of DLBCL patients were retrospectively reviewed, the CDC6 expression in DLBCL or lymph node reactive hyperplasia tissues was evaluated by immunohistochemistry. Results In silico data suggest that CDC6 overexpression is associated with inferior prognosis of DLBCL. We found that CDC6 overexpression increased SUDHL4 or OCI-LY7 cell proliferation, while knockdown of CDC6 inhibited cell proliferation in a time-dependent manner. Upon overexpression, CDC6 reduced cells in G1 phase and did not affect cell apoptosis; CDC6 knockdown led to significant cell cycle arrest in G1 phase and increase in cell apoptosis. Western blot showed that CDC6 inhibited the expression of INK4, E-Cadherin and ATR, accompanied by increased Bcl-2 and deceased Bax expression. The CDC6 protein was overexpressed DLBCL compared with lymph node reactive hyperplasia, and CDC6 overexpression was associated with non-GCB subtype, and conferred poor PFS and OS in patients with DLBCL. Conclusion CDC6 promotes cell proliferation and survival of DLBCL cells through regulation of G1/S cell cycle checkpoint and apoptosis. CDC6 is overexpressed and serves as a novel prognostic marker in DLBCL.

Abstract Background The innovative combination of all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated. Methods In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA‐ATO‐containing regimens. Results Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non‐ACA group (p = 0.032). With a median follow‐up period of 62.0 months, worse event‐free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017; p = 0.037). Conclusions To sum up, ACA remains the independent prognostic value for EFS, we should build risk‐adapted therapeutic strategies in the long‐term management of APL when such abnormalities are detected.

Alternatives to antibiotics for preventing bacteria-induced inflammation in early-weaned farm animals are sorely needed. Our previous study showed that Lactiplantibacillus plantarum L47 and inulin could alleviate dextran sulfate sodium (DSS)-induced colitis in mice. To explore the protective effects of L. plantarum L47 and inulin on the ileal inflammatory response in weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC), 28 weaned piglets were assigned into four groups, namely, CON group—orally given 10 mL/d phosphate buffer saline (PBS), LI47 group—orally given a mixture of 10 mL/d L. plantarum L47 and inulin, ECON group—orally given 10 mL/d PBS and challenged by ETEC, and ELI47 group—orally given 10 mL/d L. plantarum L47 and inulin mixture and challenged by ETEC. The results demonstrated that the combination of L. plantarum L47 and inulin reduced inflammatory responses and relieved the inflammatory damage caused by ETEC, including ileal morphological damage, reduced protein expression of ileal tight junction, decreased antioxidant capacity, and decreased anti-inflammatory factors. Transcriptome analysis revealed that L. plantarum L47 and inulin up-regulated the gene expression of phospholipase A2 group IIA (PLA2G2A) (P

Semantic feature space plays a bridging role from ‘seen classes’ to ‘unseen classes’ in zero-shot learning (ZSL). However, due to the nature of SAR distance-based imaging, which is drastically different from that of optical imaging, how to construct an appropriate semantic space for SAR ZSL is still a tricky and less well-addressed issue. In this work, three different semantic feature spaces, constructed using natural language, remote sensing optical images, and web optical images, respectively, are explored. Furthermore, three factors, i.e., model capacity, dataset scale, and pre-training, are investigated in semantic feature learning. In addition, three datasets are introduced for the evaluation of SAR ZSL. Experimental results show that the semantic space constructed using remote sensing images is better than the other two and that the quality of semantic space can be affected significantly by factors such as model capacity, dataset scale, and pre-training schemes.

To address the problem of accurately evaluating age-friendly retrofit indicators in urban communities, this study constructs an evaluation model that takes into account user preferences and their interaction needs based on the social–ecological–technological systems (SETS) theory. The model aims to establish a set of precise community retrofit indicators, covering aspects such as public participation level, public ancillary facilities, green space layout, living environment building, health service support, and accessible design. By employing prioritization strategies, the model seeks to maximize resident satisfaction and promote harmonious coexistence between the community and the environment. Firstly, the retrofit evaluation indicators are formulated using the SETS theory. The entropy weight method (EWM) is then applied to determine the initial weights of these evaluation indicators, followed by the use of the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method to analyze the interrelationships among the indicators. The Kano model is integrated to adjust the weights, reflecting their importance. The final weights of the indicators are determined through normalization. Based on this, the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method is employed to rank and analyze the importance of age-friendly retrofits in the community. Finally, six communities in Dalian, Liaoning Province, China, are selected as samples to evaluate and analyze the age-friendly retrofit indicators. Different methods are compared, and their advantages and disadvantages are ranked to validate the effectiveness and feasibility of the proposed approach. Based on the analysis results, specific design schemes for improving the identified shortcomings in age-friendly aspects of these communities are proposed, considering the needs of aging populations and taking into account community public facilities, accessible design renovations, and the enhancement of green space layouts. This study aims to explore the comprehensive benefits of an age-friendly retrofit in urban communities and provide reference for the deep integration of social, ecological, and technological benefits in urban renewal. The evaluation indicators, methods, and conclusions presented can serve as a decision-making basis for the renovation and renewal of aging urban communities, particularly in terms of age-friendly updates.

In recent years, remotely controlling an unmanned aerial vehicle (UAV) to perform coverage search missions has become increasingly popular due to the advantages of the UAV, such as small size, high maneuverability, and low cost. However, due to the distance limitations of the remote control and endurance of a UAV, a single UAV cannot effectively perform a search mission in various and complex regions. Thus, using a group of UAVs to deal with coverage search missions has become a research hotspot in the last decade. In this paper, a differential evolution (DE)-based multi-UAV cooperative coverage algorithm is proposed to deal with the coverage tasks in different regions. In the proposed algorithm, named DECSMU, the entire coverage process is divided into many coverage stages. Before each coverage stage, every UAV automatically plans its flight path based on DE. To obtain a promising flight trajectory for a UAV, a dynamic reward function is designed to evaluate the quality of the planned path in terms of the coverage rate and the energy consumption of the UAV. In each coverage stage, an information interaction between different UAVs is carried out through a communication network, and a distributed model predictive control is used to realize the collaborative coverage of multiple UAVs. The experimental results show that the strategy can achieve high coverage and a low energy consumption index under the constraints of collision avoidance. The favorable performance in DECSMU on different regions also demonstrate that it has outstanding stability and generality.

Agaricus bisporus, belonging to the genus Agaricus and the family Agaricaceae, is a popular commercially cultivated mushroom with rich nutritional and medical values. Cultivation of A. bisporus requires superior cultivars. Understanding the differences between wild and cultivated accession at the genetic level is crucial for mining loci and genes associated with cultivation-related traits, informing future breeding directions. Additionally, the identification of loci and genes associated with important agronomic traits (e.g., yield and quality) facilitates mushroom molecular breeding. In this study, we conducted sequencing of 200 strains of A. bisporus and analyzed genomic variations. Population structure and genetic relationships were investigated for 200 strains. Selection signs and genes were also obtained after selection sweep analysis. Thirteen candidate genes in the selective elimination regions had significantly different expression patterns at the fruit body stage. Moreover, six genes were identified for the esterase isozyme type through a combination of GWAS and RNA data. This study provides insight into environmental adaptation at the genetic base, providing valuable genetic resources for button mushroom molecular breeding to improve environmental adaptation, quality, or yield.

In this work, a language-level Semantics-Conditioned framework for 3D Point cloud segmentation, called SeCondPoint, is proposed, where language-level semantics are introduced to condition the modeling of the point feature distribution, as well as the pseudo-feature generation, and a feature–geometry-based Mixup approach is further proposed to facilitate the distribution learning. Since a large number of point features could be generated from the learned distribution thanks to the semantics-conditioned modeling, any existing segmentation network could be embedded into the proposed framework to boost its performance. In addition, the proposed framework has the inherent advantage of dealing with novel classes, which seems an impossible feat for the current segmentation networks. Extensive experimental results on two public datasets demonstrate that three typical segmentation networks could achieve significant improvements over their original performances after enhancement by the proposed framework in the conventional 3D segmentation task. Two benchmarks are also introduced for a newly introduced zero-shot 3D segmentation task, and the results also validate the proposed framework.

Within the genus Mycena, species exhibiting brownish basidiomata present considerable challenges in identification due to similar coloration. This study underscores the significance of pileipellis types and cheilocystidia characteristics as critical in delimiting brownish Mycena species. To clarify the principal taxonomic characters and their utility in distinguishing between brownish Mycena species, a morphological taxonomy and phylogenetic analysis were performed. Five new species from China were introduced and characterized through a comprehensive morphological anatomy and phylogenetic substantiation: M. campanulatihemisphaerica sp. nov., M. digitifurcata sp. nov., M. kunyuensis sp. nov., M. limitis sp. nov., and M. oryzifluens sp. nov. Discussions of these taxa are supplemented with morphological illustrations. The phylogenetic relationships were inferred using Bayesian Inference and Maximum Likelihood methods based on sequences from the internal transcribed spacer and the large subunit regions of nuclear ribosomal RNA. With the addition of these five new species, the worldwide count of brownish Mycena increases to 94, and a key to the 29 known species of brownish Mycena from China is presented.

Background and Purpose: Precisely assessing the likelihood of an intracranial aneurysm rupturing is critical for guiding clinical decision-making. The objective of this study is to construct and validate a deep learning framework utilizing point clouds to forecast the likelihood of aneurysm rupturing.Methods: The dataset included in this study consisted of a total of 623 aneurysms, with 211 of them classified as ruptured and 412 as unruptured, which were obtained from two separate projects within the AneuX morphology database. The HUG project, which included 124 ruptured aneurysms and 340 unruptured aneurysms, was used to train and internally validate the model. For external validation, another project named @neurIST was used, which included 87 ruptured and 72 unruptured aneurysms. A standardized method was employed to isolate aneurysms and a segment of their parent vessels from the original 3D vessel models. These models were then converted into a point cloud format using open3d package to facilitate training of the deep learning network. The PointNet++ architecture was utilized to process the models and generate risk scores through a softmax layer. Finally, two models, the dome and cut1 model, were established and then subjected to a comprehensive comparison of statistical indices with the LASSO regression model built by the dataset authors.Results: The cut1 model outperformed the dome model in the 5-fold cross-validation, with the mean AUC values of 0.85 and 0.81, respectively. Furthermore, the cut1 model beat the morphology-based LASSO regression model with an AUC of 0.82. However, as the original dataset authors stated, we observed potential generalizability concerns when applying trained models to datasets with different selection biases. Nevertheless, our method outperformed the LASSO regression model in terms of generalizability, with an AUC of 0.71 versus 0.67.Conclusion: The point cloud, as a 3D visualization technique for intracranial aneurysms, can effectively capture the spatial contour and morphological aspects of aneurysms. More structural features between the aneurysm and its parent vessels can be exposed by keeping a portion of the parent vessels, enhancing the model’s performance. The point cloud-based deep learning model exhibited good performance in predicting rupture risk while also facing challenges in generalizability.

In the past 11 years, there has been a surge in studies exploring the regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, a significant gap persists in comprehensive scientometric analysis and scientific mapping research, especially in tracking the evolution, primary contributors, and emerging research focal points. This study aims to comprehensively update the advancements in targeting ferroptosis with various TCMs during the previous 11 years. The data, covering the period from 1 January 2012, to 30 November 2023, were retrieved from the Web of Science database. For in-depth scientometric and visualized analyses, a series of advanced analytical instruments were employed. The findings highlight China’s predominant role, accounting for 71.99% of total publications and significantly shaping research in this domain. Noteworthy productivity was observed at various institutions, including Guangzhou University of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, and Zhejiang University. Thomas Efferth emerged as the foremost author within this field, while Frontiers in Pharmacology boasted the highest publication count. This study pinpointed hepatocellular carcinoma, chemical and drug-induced liver injury, mitochondrial diseases, acute kidney injury, and liver failure as the most critical disorders addressed in this research realm. The research offers a comprehensive bibliometric evaluation, enhancing our understanding of the present status of TCM therapy in managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers and newcomers by accelerating access to vital information and fostering innovative concept extraction within this specialized field.

Summary: Tumors maintain an alkaline intracellular environment to enable rapid growth. The proton exporter NHE1 participates in maintenance of this pH gradient. However, whether targeting NHE1 could inhibit the growth of tumor cells remains unknown. Here, we report that the NHE1 inhibitor Hexamethylene amiloride (HA) efficiently suppresses the growth of AML cell lines. Moreover, HA combined with venetoclax synergized to efficiently inhibit the growth of AML cells. Interestingly, lysosomes are the main contributors to the synergism of HA and venetoclax in inhibiting AML cells. Most importantly, the combination of HA and venetoclax also had prominent anti-leukemia effects in both xenograft models and bone marrow samples from AML patients. In summary, our results provide evidence that the NHE1 inhibitor HA or its combination with venetoclax efficiently inhibits the growth of AML in vitro and in vivo.

ABSTRACTAirborne transmissibility is a prerequisite for a pandemic influenza A virus (IAV), and a better understanding of how zoonotic IAV evolves to acquire a transmissible phenotype is essential for pandemic preparedness. Select contemporary influenza A(H9N2) viruses such as A/Anhui-Lujiang/39/2018 (AL/39) have exhibited a limited transmission capability by the airborne route in the ferret model; therefore, it is of great importance to identify viral factors that contribute to enhanced transmission. To investigate the role of virus acid stability in virus airborne transmission, we rescued a pair of isogenic A(H9N2) viruses, including the wild-type (wt) AL/39 and the mutant virus bearing a naturally occurring substitution HA1-Y17H, with a resulting difference in virus pH thresholds for hemagglutinin activation. We next assessed virus replication, airborne transmission, and fitness in a co-infection competition model in ferrets. We found that the HA1-Y17H mutant virus yielded only non-productive airborne transmission despite possessing a comparative replication as the wt virus in the ferret upper respiratory tract. Furthermore, ferrets inoculated with the wt virus emitted more virus-laden particles into the air than the HA1-Y17H mutant virus-inoculated animals. During ferret co-infection experiments, the wt virus was the dominant species in multiple types of specimens following different inoculation routes. Taken together, our study demonstrates that an acid-stable IAV had a greater capacity to establish a productive infection in the ferret upper respiratory tract and was emitted in greater quantities from infected animals, features that may contribute to virus airborne transmission in a synergistic manner in mammalian hosts.IMPORTANCEDespite the accumulation of evidence showing that airborne transmissible influenza A virus (IAV) typically has a lower pH threshold for hemagglutinin (HA) fusion activation, the underlying mechanism for such a link remains unclear. In our study, by using a pair of isogenic recombinant A(H9N2) viruses with a phenotypical difference in virus airborne transmission in a ferret model due to an acid-destabilizing mutation (HA1-Y17H) in the HA, we demonstrate that an acid-stable A(H9N2) virus possesses a multitude of advantages over its less stable counterpart, including better fitness in the ferret respiratory tract, more effective aerosol emission from infected animals, and improved host susceptibility. Our study provides supporting evidence for the requirement of acid stability in efficient airborne transmission of IAV and sheds light on fundamental mechanisms for virus airborne transmission.

ABSTRACTPatients with hematologic malignancies are often immunodeficient and therefore have a higher risk of severe symptoms from coronavirus disease 2019 (COVID-19). We retrospectively examined a cohort of 289 patients from 16 hospitals in Zhejiang Province who had hematologic malignancies and COVID-19 during a period when the Omicron variant was predominant. Univariate analysis showed that some clinical characteristics, including elder age (P = 0.014), multiple comorbid conditions (P = 0.011), and receipt of active antineoplastic therapy (P = 0.018) were associated with an increased risk of severe COVID-19. Patients with severe/critical COVID-19 had significantly lower levels of lymphocytes and serum albumin, and significantly higher levels of D-dimer, lactate dehydrogenase, C-reactive protein, and interleukin-6 (all P

Over the past 11 years, mounting evidence has suggested a significant association between ferroptosis and the development and progression of musculoskeletal (MSK) diseases, such as osteoporosis and osteoarthritis. However, a comprehensive bibliometric analysis summarizing the relationship between ferroptosis and MSK diseases is currently lacking. The present study collected articles and reviews on the topic of ferroptosis in MSK diseases. The data were collected from January 1st, 2012 to June 30th, 2023 by screening the Web of Science database. Various tools, including VOSviewer, CiteSpace, Pajek, the R package, and others, were used to conduct bibliometric and visualization analyses. Notably, China, the USA, and Italy emerged as primary contributors, jointly accounting for over 80 % of published documents, thereby shaping research in this domain. Among the diverse institutions, Shanghai Jiao Tong University, Soochow University, and Huazhong University of Science and Technology displayed the highest productivity levels. The most prolific authors include Sun Kai, Shang Peng, and Jing Xingzhi. Oxidative Medicine and Cellular Longevity stood out with the largest number of publications in this area. The five most significant disorders in this field are bone fractures, osteosarcoma, bone neoplasms, joint diseases, and osteoporotic fractures. This study represents an inaugural comprehensive bibliometric analysis, presenting a holistic view of the knowledge framework and developmental patterns in ferroptosis concerning MSK diseases over the previous eleven years. This information can aid researchers in acquiring a thorough grasp of this domain and offer invaluable insights for forthcoming explorations.