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The use of organochlorine and organophosphorus pesticides has been prohibited due to their highly toxicity. In recent years, pyrethroids (PYRs) have been widely used in agricultural production and the environment due to their high efficiency and stability, but the residual hazards caused by their frequent use have become increasingly prominent. 3-Phenoxybenzoic acid (3-PBA) is one of the major metabolites of PYRs, which is an environmental estrogen with great potential harms. Pesticide residues have seriously affected people’s production and life, which has attracted extensive attention from researchers. PYRs and 3-PBA degrading bacteria have been widely reported, and microbial and enzymatic degradation is recognized as an effective method for reducing or removing pesticide residues from agricultural products and the environment. The continuous development of genetic engineering and molecular biology technology provides a new way to explore methods for reducing pesticide residues. In this article, we summarize the basic properties and residual hazards of PYRs and 3-PBA, and we review the current status of PYRs residues in agricultural products and the environment as well as recent progress in research on the modes of microbial metabolism and the mechanisms of microbial adsorption and degradation of PYRs. Moreover, we give an outlook on enzymes degrading PYRs and their genetic engineering in order to provide a reference for solving the problem of pesticide residues in agricultural products and the environment.

Abstract The expression and biological function of junctional adhesion molecule-like protein (JAML) in colorectal cancer (CRC) remain unclear. Paraffin tissue samples from 50 cases of CRC were collected to determine the expression of JAML. JAML was overexpressed or knock-down in CRC cells to evaluated the proliferation, migration and invasion in vitro and in vivo. Western-blot and others were applied to explore the mechanisms. The study showed that JAML was highly expressed within cancer tissues in 50% (25/50) of patients with CRC, and was correlated with higher TNM stage (p

Abstract Background Climate change has raised scientific interest in examining the associations of weather conditions with adverse health effects, while most studies determined human thermal stress using ambient air temperature rather than the thermophysiological index. Objectives To evaluate the association between emergency ambulance dispatches (EADs) related to cardiovascular causes and heat/cold stress in Shenzhen, a city in southern China, with the aim of providing new insights for local policymakers. Methods A time series analysis using ambulance dispatch data of cardiovascular diseases in Shenzhen, China (2013–2019) was conducted. A quasi-Poisson nonlinear distributed lag model was applied to explore the relationship between emergency ambulance dispatches (EADs) due to cardiovascular causes and thermal stress (determined by Universal Thermal Climate Index, UTCI). Attributable fractions were estimated to identify which UTCI ranges have a greater health impact. Results The relationship between UTCI and EADs due to cardiovascular diseases exhibits a reverse J-shaped curve. The effects of cold stress were immediate and long-lasting, whereas the effects of heat stress were non-significant. Compared with the optimal equivalent temperature (71st percentile of UTCI, 29.22 °C), the relative risks for cumulative (0–21 days) exposures to cold stress (1st percentile, − 0.13 °C; 5th percentile, 7.68 °C) were 1.55 (95%CI:1.28,1.88) and 1.44 (95%CI:1.22,1.69), respectively. Thermal (cold and heat) stress was responsible for 10.81% (95%eCI: 5.67%,15.43%) of EADs for cardiovascular diseases, with 9.46% (95%eCI: 3.98%,14.40%) attributed to moderate cold stress (2.5th ~ 71st percentile). Greater susceptibility to cold stress was observed for males and the elderly. Heat stress showed harmful effects in the warm season. Conclusions Our results demonstrated that cold exposure elevates the risk of EADs for cardiovascular causes in Shenzhen, and moderate cold stress cause the highest burden of ambulance dispatches. Health authorities should consider effective adaptation strategies and interventions responding to cold stress to reduce the morbidity of cardiovascular diseases.

Abstract In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.

Abstract Objective The aim of this study was to investigate the effect of patellar denervation (PD) on pain, function and ability to kneel after unicompartmental knee arthroplasty (UKA). Methods Patients with medial knee osteoarthritis who underwent UKA were prospectively selected. Patients were randomly divided into PD and non-PD groups based on whether patellar denervation was performed. Clinical assessment was performed using the Hospital for Special Surgery (HSS) knee score, Kujiala score, visual analogue scale (VAS) and forgotten joint score (FJS-12), as well as postoperative complications were recorded. The patients’ postoperative self-perception and actual ability to perform different kneeling positions were assessed in the two groups. Results UKA patients treated with PD achieved better Kujiala scores and FJS-12 scores, reduced anterior knee pain and improved kneeling ability postoperatively, validating the effectiveness of PD in UKA. Perception and actual performance of kneeling remained mismatched in PD patients, but performance during different kneeling activities was generally better than in non-PD patients. Trial registration Clinical Trial Registration: ChiCTR1900025669. Conclusion Patellar denervation can safely and effectively improve patellofemoral joint function, pain and kneeling ability in the early postoperative period after UKA.

Gastric cancer ranks fifth in global cancer mortality, which is highly aggressive and heterogeneous. However, the research and treatment of gastric cancer is hindered by short of research models that may characterize the developmental properties of gastric cancer. Gastric cancer organoid is a multicellular three-dimensional structure developed in vitro, which can mimic the structure and function of native gastric cancer. Gastric cancer organoids have great application potential and development prospects in establishing gastric cancer research models, mimicking the tumor microenvironment, high-throughput screening of drugs, discovering new therapeutic targets, predicting clinical therapeutic responses, and guiding individualized treatment. In this paper, the progress of gastric cancer organoids in basic research and clinical application is reviewed aiming for promoting the progress of preclinical research and supporting the clinical treatment of gastric cancer.

Cancer stem cells (CSCs) play a pivotal role in tumor initiation, proliferation, metastasis, drug resistance, and recurrence. Consequently, targeting CSCs has emerged as a promising avenue for cancer therapy. Recently, 3-phosphoglycerate dehydrogenase (PHGDH) has been identified as being intricately associated with the regulation of numerous cancer stem cells. Yet, reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are limited. In this study, the novel “molecular glue” LXH-3-71 was identified, and it robustly induced degradation of PHGDH, thereby modulating the stemness of colorectal cancer cells (CRCs) both in vitro and in vivo. Remarkably, LXH-3-71 was observed to form a dynamic chimera, between PHGDH and the DDB1-CRL E3 ligase. These insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH inhibitors. Additionally, compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase, facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

Abstract Background Totally robotic distal gastrectomy (TRDG) is being used more and more in gastric cancer (GC) patients. The study aims to evaluate the short-term efficacy of TRDG and robotic-assisted distal gastrectomy (RADG) in the treatment of GC. Methods We retrospectively collected the clinical data of patients who underwent TRDG or RADG, of which 60 patients were included in the study: 30 cases of totally robotic and 30 cases of robotic-assisted. The short-term efficacy of the two groups was compared. Results There was no significant difference in the clinicopathological data between the two groups. Compared to RADG, TRDG had less intraoperative blood loss(P = 0.019), less postoperative abdominal drainage(P = 0.031), shorter time of exhaust( P = 0.001) and liquid diet(P = 0.001), shorter length of incision(P

Abstract Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

The single value fluctuation of impact work occurs frequently in high strength steel, especially for medium or super thick plates. With respect to the single value fluctuation of impact work in 700 MPa low alloy thin tempered plate, the present study carried out a comprehensive and comparative analysis through metallographic microstructure, second-phase precipitated particle and inclusion distribution. The results show that the microstructure type, grain boundary ratio of HAGBs/LAGBs, grain size and orientation of the specimens with 37 J and 7 J impact work are basically the same. The two specimens show excellent process-microstructure consistency, which fully indicate that the temperature fields of the two specimens are consistent. Since the temperature field is basically the same, the (Ti, Nb, Mo)C compound precipitated particles in the two specimens maintain a good Baker-Nutting relationship with the matrix, and the interface between the precipitated particles and the matrix maintain a stable coherent/semi-coherent relationship. The main reason for the decrease of impact work of tempered plate is related to the distribution of inclusions. There are more spherical and square large size inclusion particles and microcracks in the specimen with lower impact work. Among them, the large square inclusion particles dominate mostly. And with the increase of the plastic deformation degree of the metal matrix, the large square inclusion has an obvious evolution by separation from the matrix to forming microcracks, and then to fracture.

Olfaction, the sense of smell, is crucial for animal survival, especially in localizing prey or food. However, little is known about the fish behavioral responses to specific food odors and which olfactory receptor might be activated by the food odors. Here, we examined the evolutionary relationships and classified the subfamilies of olfactory receptors (ORs), and conducted behavioral and gene expression analysis in grass carp (Ctenopharyngodon idellus). We identified 196 intact ORs in the grass carp genome and classified them into 8 subfamilies: β, δ, ε, η, γ, κ, θ, and ζ. 12 representative ORs (4 β, 4 δ, and 4 ε) were highly expressed in the olfactory epithelium (OE) of 24-month-old grass carp. Behavioral exploration found that grass carp showed different behaviors to different food odors at a series of concentrations. Specifically, 0.01 μmol/L amino acid mixtures and 0.005 × Hydrilla verticillata extracts strongly changed the preference index and swimming trajectories in 6-month-old grass carp. In addition, the two food odors stimulation differentially induced ORs expression in three tissues, especially strong in the olfactory bulb and brain. Altogether, our results suggest that olfaction plays an important role in the regulation of fish feeding behavior and provide a basis for further studies on the function and specific recognition of olfactory receptors in fish.

Abstract The success of current deep learning models depends on a large number of precise labels. However, in the field of medical image segmentation, acquiring precise labels is labor-intensive and time-consuming. Hence, the challenge of achieving a high-performance model via datasets containing noisy labels has attracted significant research interest. Some existing methods are unable to exclude samples containing noisy labels and some methods still have high requirements on datasets. To solve this problem, we propose a noisy label learning method for medical image segmentation using a mixture of high and low quality labels based on the architecture of mean teacher. Firstly, considering the teacher model’s capacity to aggregate all previously learned information following each training step, we propose to leverage a teacher model to correct noisy label adaptively during the training phase. Secondly, to enhance the model’s robustness, we propose to infuse feature perturbations into the student model. This strategy aims to bolster the model’s ability to handle variations in input data and improve its resilience to noisy labels. Finally, we simulate noisy labels by destroying labels in two medical image datasets: the Automated Cardiac Diagnosis Challenge (ACDC) dataset and the 3D Left Atrium (LA) dataset. Experiments show that the proposed method demonstrates considerable effectiveness. With a noisy ratio of 0.8, compared with other methods, the mean Dice score of our proposed method is improved by 2.58% and 0.31% on ACDC and LA datasets, respectively.

Abstract Background Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015–2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life’s Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. Results In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. Conclusion Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

In the process of launching guided projectile under the conventional system, it is difficult to effectively obtain the precise navigation parameters of the projectile in the high dynamic environment. Aiming at this problem, this paper describes a new system of guided ammunition based on tail spin reduction. After analyzing the mechanism of the ammunition's tail spin reduction, a navigation method of large scale difference tail control simple guided ammunition based on speed constraint is proposed. In this method, the corresponding navigation constraints can be carried out by combining the rotation speed state of the ammunition itself, and the optimal solution of navigation parameters during the flight of the missile can be obtained by Extended Kalman Filter (EKF). Finally, the performance of the proposed method was verified by the simulation environment, and the hardware-in-the-loop simulation test and flight test were carried out to verify the performance of the method in the real environment. The experimental results show that the proposed method can achieve the optimal estimation of navigation parameters for simple guided ammunition with large-scale difference tail control. Under the conditions of simulation test and hardware-in-loop simulation test, the position and velocity errors calculated by the method in this paper converged. Under the condition of flight test, the spatial average error calculated by the method described in this paper is 6.17 m, and the spatial error of the final landing point is 3.50 m. Through this method, the accurate acquisition of navigation parameters in the process of projectile launching is effectively realized.

Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Objective Uniportal full‐endoscopic foraminotomy offers a promising alternative to conventional surgical methods for individuals afflicted by lumbar foraminal stenosis. This study aims to evaluate the efficacy and clinical outcomes of uniportal full‐endoscopic foraminotomy in patients diagnosed with lumbar foraminal stenosis. Methods A comprehensive retrospective analysis was conducted on individuals who underwent full‐endoscopic foraminotomy in our medical center, between January 2018 and December 2019. The investigation encompassed the demographic data of patients and key clinical metrics such as the visual analogue scale of leg (VAS‐L) and back pain (VAS‐B), Oswestry disability index (ODI) scores, the Short Form‐36 Health Survey physical component summary (SF‐36 PCS) and the mental component summary (SF‐36 MCS), as well as modified MacNab grades, were systematically assessed and compared. Furthermore, radiological parameters: Coronal Cobb angle (CCA), Intervertebral angle changes (IAC), Disc height index (DHI), the foraminal cross‐sectional area (FCSA) and the FCSA enlargement ratio were also compared. A variety of statistical analyses including Student t‐test, chi‐square tests, Fisher's exact tests, Pearson's and Spearman's correlation analyses, and Interclass Correlation Coefficients (ICCs) were employed. Results 64 patients, including 34 males and 30 females were enrolled. The mean follow‐up period extended to 22.66 ± 7.05 months. Distribution by affected segments revealed 26.6% at L4‐5, 67.1% at L5‐S1 level, and 6.25% at both L4‐L5 and L5‐S1 levels. At the final follow‐up, VAS‐L decreased from 7.26 ± 1.19 to 1.37 ± 1.25, while VAS‐B decreased from 6.95 ± 0.54 to 1.62 ± 1.13 (p < 0.001). ODI score also demonstrated a substantial decrease from 74.73 ± 8.68 to 23.27 ± 8.71 (p < 0.001). Both SF‐36 PCS and SF‐36 MCS scores improved significantly (p < 0.001). Modified MacNab criteria revealed 58 excellent‐good patients (90.7%), and 6 fair‐poor patients (9.3%). No significant differences were founded in the CCA (p = 0.1065), IAC (p = 0.5544), and DHI (p = 0.1348) between pre‐operation and the final follow‐up. However, the FCSA significantly increased from 73.41 ± 11.75 to 173.40 ± 18.62 mm2 (p < 0.001), and the enlargement ratio was 142.9% ± 49.58%. Notably, the final follow‐up FCSA and the FCSA enlargement ratio were found to be larger in the excellent and good group compared to the fair and poor group, according to the modified MacNab criteria. Conclusion The utilization of uniportal full‐endoscopic foraminotomy has demonstrated its safety and efficacy in addressing lumbar foraminal stenosis. The clinical success of this procedure appears to be closely associated with the radiological decompression of the intervertebral foramen area. Importantly, the application of this technology does not seem to compromise the overall stability of the lumbar region.

Abstract The security of wireless sensor networks is a hot topic in current research. Game theory can provide the optimal selection strategy for attackers and defenders in the attack-defense confrontation. Aiming at the problem of poor generality of previous game models, we propose a generalized Bayesian game model to analyze the intrusion detection of nodes in wireless sensor networks. Because it is difficult to solve the Nash equilibrium of the Bayesian game by the traditional method, a parallel particle swarm optimization is proposed to solve the Nash equilibrium of the Bayesian game and analyze the optimal action of the defender. The simulation results show the superiority of the parallel particle swarm optimization compared with other heuristic algorithms. This algorithm is proved to be effective in finding optimal defense strategy. The influence of the detection rate and false alarm rate of nodes on the profit of defender is analyzed by simulation experiments. Simulation experiments show that the profit of defender decreases as false alarm rate increases and decreases as detection rate decreases. Using heuristic algorithm to solve Nash equilibrium of Bayesian game provides a new method for the research of attack-defense confrontation. Predicting the actions of attacker and defender through the game model can provide ideas for the defender to take active defense.

Abstract Background Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response. Methods In this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform. Results Our proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of ‘hot tumor’ phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes. Conclusion The study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.

Abstract Background Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. Methods We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. Results The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and

Abstract Background To evaluate the efficiency of artificial intelligence (AI)-assisted diagnosis system in the pulmonary nodule detection and diagnosis training of junior radiology residents and medical imaging students. Methods The participants were divided into three groups. Medical imaging students of Grade 2020 in the Jinzhou Medical University were randomly divided into Groups 1 and 2; Group 3 comprised junior radiology residents. Group 1 used the traditional case-based teaching mode; Groups 2 and 3 used the ‘AI intelligent assisted diagnosis system’ teaching mode. All participants performed localisation, grading and qualitative diagnosed of 1,057 lung nodules in 420 cases for seven rounds of testing after training. The sensitivity and number of false positive nodules in different densities (solid, pure ground glass, mixed ground glass and calcification), sizes (less than 5 mm, 5–10 mm and over 10 mm) and positions (subpleural, peripheral and central) of the pulmonary nodules in the three groups were detected. The pathological results and diagnostic opinions of radiologists formed the criteria. The detection rate, diagnostic compliance rate, false positive number/case, and kappa scores of the three groups were compared. Results There was no statistical difference in baseline test scores between Groups 1 and 2, and there were statistical differences with Group 3 (P = 0.036 and 0.011). The detection rate of solid, pure ground glass and calcified nodules; small-, medium-, and large-diameter nodules; and peripheral nodules were significantly different among the three groups (P

Objective The present study evaluated the effect of flaxseed meal degraded by a protease, Lactobacillus plantarum, or both on the growth performance, nutrient digestibility, and health status of broilers. Methods There were four diets containing flaxseed meals in its non-degraded form (control, CON), degraded with 3,000 U/kg of protease (enzymatic, ELM), 1.0×109 CFU/kg of Lactobacillus plantarum (fermented, FLM), or both (dual-degraded, DLM). Each form of flaxseed meals was added at 15% of diet. A total of 480 yellow-feathered broilers at 22 d of age were distributed into 4 groups with 6 replicates of 20 chickens each. The feeding trial lasted for 42 d. Growth performance, apparent fecal digestibility (dry matter, energy, crude protein, and ash), and serum immunoglobins and antioxidases were determined at 42 and 63 d of age. Results Results showed that ELM, FLM, and DLM increased (p

This study investigates the influence of accumulative roll bonding (ARB) cycles on the microstructure and room temperature (RT) mechanical properties of AT31/ATX3105 magnesium (Mg) alloy composite sheet. It is observed that, as the number of rolling passes increases, the interface between ATX3105 and AT31 layers exhibits stronger bonding. Furthermore, after five cycles of ARB treatment, the grain sizes of AT31 and ATX3105 layers are refined to ∼5.1 μm and ∼4.2 μm, respectively. With the increasing number of ARB passes, the strength of the composite sheets gradually increased, while their ductility showed a wave-like trend. It is particularly noteworthy that the ductility reached an optimal level of ∼17.0% after four ARB cycles. The composite sheet after five ARB cycles demonstrates the best comprehensive mechanical properties, with yield strength (YS), ultimate tensile strength (UTS), and elongation (EL) at ∼ 205.4 MPa, ∼274.9 MPa and ∼15.4%, respectively. The strength improvement mainly comes from grain boundary strengthening and heterogeneous deformation-induced (HDI) strengthening due to the layered grain structure of alternating coarse and fine grains. The results of hetero-structured Mg alloy sheet produced by ARB provides a reference for the development of Mg alloy sheet with good mechanical properties.

While carbon dioxide (CO2) is a major greenhouse gas, it is also an important C1 resource. In the trend of energy conservation and emission reduction, electrocatalytic reduction has become a very promising strategy for CO2 utilization because it can convert CO2 directly to high-valued chemicals and fuels under mild conditions. In particular, the product CO and by-product H2 can be combined into syngas by an electrocatalytic CO2 reduction reaction (CO2RR) in an aqueous medium. Different molar ratios of CO and H2 may be used to produce essential bulk chemicals or liquid fuels such as methanol, alkanes, and olefins through thermochemical catalysis, Fischer–Tropsch synthesis, microbial fermentation, and other techniques. This work discusses the latest strategies in controlling the molar ratio of CO/H2 and improving the yield of CO2RR-to-syngas. The challenges of electrocatalytic syngas production are analyzed from an industrial application perspective, and the possible measures to overcome them are proposed in terms of new catalyst design, electrolyte innovation, flow reactor optimization, anodic reaction coupling, and operando technique application.

In this study, the effects of Trichoderma erinaceum M6-5 volatile components on metabolites, respiration and energy metabolism of Alternaria alternata from postharvest Korla fragrant pear were investigated. Non-targeted metabolomics based on liquid chromatography-mass spectrometry (LC-MS) was used to determine the changes of metabolites in A. alternata after treatment with M6-5 volatile substances. At 0, 3, 5 and 7 days after fumigation with M6-5 volatile substances, the respiratory rate of A. alternata was measured, and the respiration inhibition rate were calculated. The levels of ATP, ADP, AMP and energy charge in the M6-5-treated and control groups as a function of culture time were determined by liquid chromatography (LC). The results showed that among the identified differential metabolites, 6-amyl-2h-pyrano-2-one (6pp), 4-ethylbenzaldehyde, 3,4-dimethylbenzoic acid, 4-phenylbutyric acid and 2-methoxyresorcinol were up-regulated, while 6-aminonicotinamide, 11-ketoacetyl cholesterol, 3-hydroxyconilone, jasmonic acid and benzoylsphenine were down-regulated by M6-5 volatile substances. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the significantly differential pathway was involved in the biosynthesis of secondary metabolites. At the end of the 7 day incubation period, the respiration inhibition rate of A. alternata by M6-5 volatile substances was (49.64 ± 2.04)%. Compared with the control group, treatment with M6-5 volatile substances significantly reduced the levels of ATP, ADP, AMP and energy charge, indicating that it can keep the energy charge at lower levels, thereby resulting in imbalanced energy metabolism and inhibited respiratory rate and affecting metabolite changes.

Objective To evaluate the value of mean reticulated hemoglobin content (Mchr) in diagnosing iron deficiency anemia (IDA) and assessing its severity. Methods This study included 302 patients with IDA from January 2021 to December 2021, recruited from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (North), Xinhua Hospital, and Ruijin Hospital. The cohort comprised 118 patients with mild anemia, 159 with moderate anemia, and 25 with severe anemia. In addition, 365 non-IDA patients (encompassing those with thalassemia, megaloblastic anemia, pure red cell aplastic anemia, hemolytic anemia, and aplastic anemia) and 138 healthy controls were included. Venous blood samples were collected from all participants for analysis of hemoglobin (Hb), hematocrit (HCT), Mchr, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron (Fe), transferrin saturation (TS), ferritin, and total iron-binding capacity (TIBC). Mchr levels were compared between the IDA and non-IDA patient groups and between different degrees of IDA severity. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of Mchr in IDA. Results Compared with the non-IDA group, the IDA cohort exhibited significantly reduced levels of Mchr, Hb, MCV, MCH, MCHC, HCT, Fe, TS, and ferritin, while TIBC was markedly elevated, with all differences being statistically significant (P65.8 μmol/L) were 90.76% and 94.70% respectively, and the AUC was 0.9839(95%CI: 0.9772-0.9905). Conclusions Mchr can serve as a potential clinical marker for screening IDA and its severity. Its combination with iron metabolism indicators adds diagnostic value for IDA, providing a strong basis for whether further invasive diagnosis is needed.

Abstract Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome‐driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.

Abstract Colon cancer ranks as the third most prevalent form of cancer globally, with chemotherapy remaining the primary treatment modality. To mitigate drug resistance and minimize adverse effects associated with chemotherapy, selection of appropriate adjuvants assumes paramount importance. Caffeic acid phenethyl ester (CAPE), a naturally occurring compound derived from propolis, exhibits a diverse array of biological activities. We observed that the addition of CAPE significantly augmented the drug sensitivity of colon cancer cells to oxaliplatin. In SW480 and HCT116 cells, oxaliplatin combined with 10 µM CAPE reduced the IC50 of oxaliplatin from 14.24 ± 1.03 and 84.16 ± 3.02 µM to 2.11 ± 0.15 and 3.92 ± 0.17 µM, respectively. We then used proteomics to detect differentially expressed proteins in CAPE-treated SW480 cells and found that the main proteins showing changes in expression after CAPE treatment were p62 (SQSTM1) and LC3B (MAP1LC3B). Gene ontology analysis revealed that CAPE exerted antitumor and chemotherapy-sensitization effects through the autophagy pathway. We subsequently verified the differentially expressed proteins using immunoblotting. Simultaneously, the autophagy inhibitor bafilomycin A1 and the mCherry-EGFP-LC3 reporter gene were used as controls to detect the effect of CAPE on autophagy levels. Collectively, the results indicate that CAPE may exert antitumor and chemotherapy-sensitizing effects by inhibiting autophagy, offering novel insights for the development of potential chemosensitizing agents.

Abstract Background The treatment of infected bone defects remains a clinical challenge. With the development of three-dimensional printing technology, three-dimensional printed implants have been used for defect reconstruction. The aim of this study was to investigate the clinical outcomes of three-dimensional printed porous prosthesis in the treatment of femoral defects caused by osteomyelitis. Methods Eleven patients with femoral bone defects following osteomyelitis who were treated with 3D-printed porous prosthesis at our institution between May 2017 and July 2021, were included. Eight patients were diagnosed with critical-sized defects, and the other three patients were diagnosed with shape-structural defects. A two-stage procedure was performed for all patients, and the infection was eradicated and bone defects were occupied by polymethylmethacrylate spacer during the first stage. The 3D-printed prosthesis was designed and used for the reconstruction of femoral defects in the second stage. Position of the reconstructed prostheses and bone growth were measured using radiography. The union rate, complications, and functional outcomes at the final follow-up were assessed. Results The mean length of the bone defect was 14.0 cm, union was achieved in 10 (91%) patients. All patients showed good functional performance at the most recent follow-up. In the critical-sized defect group, one patient developed a deep infection that required additional procedures. Two patients had prosthetic dislocations. Radiography demonstrated good osseous integration of the implant–bone interface in 10 patients. Conclusion The 3D printed prostheses enable rapid anatomical and mechanically stable reconstruction of extreme femur bone defects, effectively shortens treatment time, and achieves satisfactory clinical outcomes.

Abstract Background Evidence suggests that radiotherapy is a potent immunomodulator in non-small cell lung cancer (NSCLC). Conversely, it has rarely been demonstrated if immune infiltration can influence radiotherapy efficacy. Herein, we explored the effect of tumor-infiltrating lymphocytes (TILs) on the response to postoperative radiotherapy (PORT) in completely resected stage III-pN2 NSCLC. Methods This retrospective study included 244 patients with pathologically confirmed stage III-N2 NSCLC who underwent complete resection at our institution between 2014 and 2020. TILs were assessed with permanent full-face hematoxylin and eosin (H&E) sections and the evaluation of TILs was based on a published guideline. Patients were stratified into the TILlow or TILhigh group with a cutoff value of 50%. Kaplan-Meier method and Log‐rank test were utilized to assess disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression analysis were conducted to determine prognostic indicators. Results Among 244 patients, a total of 121 patients received PORT whereas 123 did not. TILs level in patients with PORT was significantly higher than that in patients without PORT (p

Abstract Cryptophytes are ancestral photosynthetic organisms evolved from red algae through secondary endosymbiosis. They have developed alloxanthin-chlorophyll a/c2-binding proteins (ACPs) as light-harvesting complexes (LHCs). The distinctive properties of cryptophytes contribute to efficient oxygenic photosynthesis and underscore the evolutionary relationships of red-lineage plastids. Here we present the cryo-electron microscopy structure of the Photosystem II (PSII)–ACPII supercomplex from the cryptophyte Chroomonas placoidea. The structure includes a PSII dimer and twelve ACPII monomers forming four linear trimers. These trimers structurally resemble red algae LHCs and cryptophyte ACPI trimers that associate with Photosystem I (PSI), suggesting their close evolutionary links. We also determine a Chl a-binding subunit, Psb-γ, essential for stabilizing PSII–ACPII association. Furthermore, computational calculation provides insights into the excitation energy transfer pathways. Our study lays a solid structural foundation for understanding the light-energy capture and transfer in cryptophyte PSII–ACPII, evolutionary variations in PSII–LHCII, and the origin of red-lineage LHCIIs.

Abstract Purpose Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis. Methods A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood. Results In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments. Conclusion The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

Abstract Background Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying patients who may benefit from ICIs is currently a challenge. Methods 47 tumor patients harboring ARID1A mutations were retrospectively studied. The genomic profiling data through next-generation sequencing (NGS) and relevant clinical information were collected and analyzed. Additionally, bioinformatics analysis of the expression of immune checkpoints and immune cell infiltration levels was conducted in ARID1A-mutant gastric cancer (GC). Results ARID1A mutations frequently co-occur with mutations in DNA damage repair (DDR)-associated genes. Among the 35 ARID1A-mutant patients who received immunotherapy, 27 were evaluable., with the objective response rate (ORR) was 48.15% (13/27), and the disease control rate (DCR) was 92.59% (25/27). Moreover, survival assays revealed that ARID1A-mutant patients had longer median overall survival (mOS) after immunotherapy. In ARID1A-mutated GC patients, receiving ICIs treatment indicated longer progressive-free survival (PFS). Additionally, the incidence of microsatellite instability-high (MSI-H), high tumor mutation burden (TMB-H) and Epstein‒Barr virus (EBV) infection was elevated. Bioinformatic analysis showed significant enrichment of immune response and T cell activation pathway within differentially expressed genes in ARID1A-mutant GC group. Finally, ARID1A mutations status was considered to be highly correlated with the level of tumor infiltrating lymphocytes (TILs) and high expression of immune checkpoints. Conclusions Patients with tumors harboring ARID1A mutations may achieve better clinical outcomes from immunotherapy, especially in GC. ARID1A mutations can lead to genomic instability and reshape the tumor immune microenvironment (TIME), which can be used as a biomarker for immunotherapy.

Abstract Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.

This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photinia microphylla (J.E.Vidal) B.B.Liu and Weniomeles atropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.

Abstract Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R tdTomato mice to lethally irradiated Ackr1 −/− mice (Ackr1 −/− chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Abstract As one of the most attractive methods for the synthesis of ordered hierarchically porous crystalline materials, the soft-template method has not appeared in covalent organic frameworks (COFs) due to the incompatibility of surfactant self-assembly and guided crystallization process of COF precursors in the organic phase. Herein, we connect the soft templates to the COF backbone through ionic bonds, avoiding their crystallization incompatibilities, thus introducing an additional ordered arrangement of soft templates into the anionic microporous COFs. The ion exchange method is used to remove the templates while maintaining the high crystallinity of COFs, resulting in the construction of COFs with ordered hierarchically micropores/mesopores, herein named OHMMCOFs (OHMMCOF-1 and OHMMCOF-2). OHMMCOFs exhibit significantly enhanced functional group accessibility and faster mass transfer rate. The extrinsic porosity can be adjusted by changing the template length, concentration, and ratio. Cationic guanidine-based COFs (OHMMCOF-3) are also constructed using the same method, which verifies the scalability of the soft-template strategy. This work provides a path for constructing ordered and tunable extrinsic porosity in COFs with greatly improved mass transfer efficiency and functional group accessibility.

BackgroundTelemedicine provides remote health care services to overcome constraints of time and space in accessing medical care. Similarly, internet hospitals in China support and provide remote health care services. Due to the COVID-19 pandemic, there has been a proliferation of internet hospitals. Many new services, including online consultations and regular online follow-up visit services, can now be accessed via internet hospitals in China. However, the accessibility, cost, and quality advantages of regular online follow-up visit services remain unclear. ObjectiveThis study aimed to evaluate the accessibility, costs, and quality of an online regular follow-up visit service provided by an internet hospital in China. By analyzing the accessibility, costs, and quality of this service from the supply and demand sides, we can summarize the practical and theoretical experiences. MethodsA mixed methods study was conducted using clinical records from 18,473 patients receiving 39,239 online regular follow-up visit services at an internet hospital in 2021, as well as interviews with 7 physicians, 2 head nurses, and 3 administrative staff members. The quantitative analysis examined patient demographics, diagnoses, prescriptions, geographic distribution, physician characteristics, accessibility (travel time and costs), and service hours. The qualitative analysis elucidated physician perspectives on ensuring the quality of online health care. ResultsPatients were predominantly middle-aged men with chronic diseases like viral hepatitis who were located near the hospital. The vast majority were from Guangdong province where the hospital is based, especially concentrated in Guangzhou city. The online regular follow-up visit service reduced travel time by 1 hour to 9 hours and costs by ¥6 to ¥991 (US $0.86-$141.32) depending on proximity, with greater savings for patients farther from the hospital. Consultation times were roughly equivalent between online and in-person visits. Physicians provided most online services during lunch breaks (12 PM to 2 PM) or after work hours (7 PM to 11 PM), indicating increased workload. The top departments providing online regular follow-up visit services were Infectious Diseases, Rheumatology, and Dermatology. The most commonly prescribed medications aligned with the prevalent chronic diagnoses. To ensure quality, physicians conducted initial in-person consultations to fully evaluate patients before allowing online regular follow-up visits, during which they communicated with patients to assess conditions and determine if in-person care was warranted. They also periodically reminded patients to come in person for more comprehensive evaluations. However, they acknowledged online visits cannot fully replace face-to-face care. ConclusionsTelemedicine services such as online regular follow-up visit services provided by internet hospitals must strictly adhere to fundamental medical principles of diagnosis, prescription, and treatment. For patients with chronic diseases, online regular follow-up visit services improve accessibility and reduce cost but cannot fully replace in-person evaluations. Physicians leverage various strategies to ensure the quality of online care.

ABSTRACT Carboxysomes are proteinaceous organelles featuring icosahedral protein shells that enclose the carbon-fixing enzymes, ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco), along with carbonic anhydrase. The intrinsically disordered scaffolding protein CsoS2 plays a vital role in the construction of α-carboxysomes through bridging the shell and cargo enzymes. The N-terminal domain of CsoS2 binds Rubisco and facilitates Rubisco packaging within the α-carboxysome, whereas the C-terminal domain of CsoS2 (CsoS2-C) anchors to the shell and promotes shell assembly. However, the role of the middle region of CsoS2 (CsoS2-M) has remained elusive. Here, we conducted in-depth examinations on the function of CsoS2-M in the assembly of the α-carboxysome shell by generating a series of recombinant shell variants in the absence of cargos. Our results reveal that CsoS2-M assists CsoS2-C in the assembly of the α-carboxysome shell and plays an important role in shaping the α-carboxysome shell through enhancing the association of shell proteins on both the facet-facet interfaces and flat shell facets. Moreover, CsoS2-M is responsible for recruiting the C-terminal truncated isoform of CsoS2, CsoS2A, into α-carboxysomes, which is crucial for Rubisco encapsulation and packaging. This study not only deepens our knowledge of how the carboxysome shell is constructed and regulated but also lays the groundwork for engineering and repurposing carboxysome-based nanostructures for diverse biotechnological purposes.IMPORTANCECarboxysomes are a paradigm of organelle-like structures in cyanobacteria and many proteobacteria. These nanoscale compartments enclose Rubisco and carbonic anhydrase within an icosahedral virus-like shell to improve CO2 fixation, playing a vital role in the global carbon cycle. Understanding how the carboxysomes are formed is not only important for basic research studies but also holds promise for repurposing carboxysomes in bioengineering applications. In this study, we focuses on a specific scaffolding protein called CsoS2, which is involved in facilitating the assembly of α-type carboxysomes. By deciphering the functions of different parts of CsoS2, especially its middle region, we provide new insights into how CsoS2 drives the stepwise assembly of the carboxysome at the molecular level. This knowledge will guide the rational design and reprogramming of carboxysome nanostructures for many biotechnological applications.

Skeletal muscle atrophy was one of main complications of type 2 diabetes mellitus. Hydrogen sulfide (H2S) is involved in various physiological functions, such as anti-hypertension and anti-oxidant. Skeletal muscle atrophy caused by type 2 diabetes could lead to the regeneration of muscle fibers. Wnt signaling pathway plays a crucial important role in this process. H2S maybe regulate the Wnt signaling pathway to alleviate skeletal muscle atrophy, however, this role has not been clarified. The aim of this study is to investigate the potential regulatory role of H2S in the Wnt signaling pathway. C2C12 myoblasts treated with 500 μmol palmitate as an in vitro model. Western blot was used to detect the levels of CSE, PKM1, β-catenin, MuRF1, MYOG, MYF6 and MYOD1. In addition, MuRF1 was mutated at Cys44 and MuRF1 S-sulfhydration was detected by biotin switch assay. The interaction between PKM1 and MuRF1 was assessed via Co-immunoprecipitation. Differentiation of C2C12 myoblasts was evaluated using LAMININ staining. These data showed the levels of CSE, β-catenin, PKM1, MYOG, MYF6 and MYOD1 were decreased in pal group, compared with control and pal + NaHS groups. MuRF1 Cys44 mutants increased the protein levels of β-catenin, MYOG, MYF6 and MYOD1 in pal group. Our results suggest that H2S regulates the S-sulfhydration levels of MuRF1 at Cys44, influencing the ubiquitination levels of PKM1 and ultimately promoting myoblast differentiation.

The biomass production as well as the accumulation of secondary metabolites of plant is highly determined by the absorption of nutritional elements, in particular nitrogen (N) and phosphorus (P). Arbuscular mycorrhizal fungi (AMF) can absorb soluble P and transport it to plants, while phosphate solubilizing bacteria (PSB) can increase the content of solubilizing P in soil. Previous studies have identified the effects of either AMF or PSB inoculation on altering plant C:N:P stoichiometry, whether AMF interact with PSB in promoting plant growth and changing elemental concentration and composition of secondary metabolites by altering plant C:N:P stoichiometry remains ambiguous. In this study, we investigated the effects of inoculation of AMF, PSB, and their co-inoculation AMP (AMF and PSB) on the biomass growth, the C:N:P stoichiometry, the core microorganisms of rhizosphere soil, and the ginsenoside compositions of ginseng (Panax ginseng). The results showed that compared to control or single inoculation of AMF or PSB, co-inoculation of AMF and PSB significantly increased the AMF colonization rate on ginseng roots, increased the biomass of both above and under-ground parts of ginseng. Similarly, co-inoculation of AMF and PSB substantially increased the concentrations of N and P, reduced the ratios of C:P and N:P in the above-ground part of ginseng. The co-inoculation of AMF and PSB also increased concentrations of total ginsenosides and altered the compositions of ginsenosides in both the above and under-ground parts of ginseng. Analysis the rhizosphere microorganism showed that the co-inoculation of AMF and PSB recruited distinct core microorganisms that differ from the control and treatments with single inoculation of AMF or PSB. Our results suggested that PSB inoculation enhanced the positive effect of AMF in improving the absorption of nutrimental elements, altered the C:N:P stoichiometry and, ginsenosides concentration and composition of ginseng, influenced the plant rhizosphere microbial community. These findings offer valuable insights into enhancing plant biomass production and promoting secondary metabolites by improving the plant-fungi-bacterial relationships.

The successful launch of the Sentinel-1 satellite in 2014 brought a large amount of free SAR images to researchers and scholars, and its application in the fields of ocean monitoring, land use change, natural disaster monitoring and emergency response is becoming increasingly mature and precise. The main applications of InSAR can be categorized into surface deformation monitoring and DEM generation. Sentinel-1 was initially designed for surface deformation monitoring; thus, there are fewer relevant studies on the use of Sentinel-1 data for DEM extraction. However, as the only SAR satellite whose data are currently free and openly available and whose data are constantly updated, it is highly important to study its sources of error in the DEM generation process and the accuracy of its products. In addition, the SAR data provided by the Sentinel-1 satellite has the advantages of high resolution, all-day, all-weather, providing a large data source for DEM production. Taking the Ankang area as an example, this paper analyzes the influence of the InSAR spatiotemporal baseline, ground cover, terrain factors, SAR imaging and other factors on the accuracy of the Sentinel-1-extracted DEM using multisource ground observation data to validate its feasibility for terrain mapping in complex terrain. Finally, we look forward to how to effectively improve the quality of Sentinel-1 DEM products to provide guidance and a reference for subsequent research on DEM extraction using Sentinel-1 SAR images and designation of Sentinel-1 C satellite’s parameters.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

Summary: Background: Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study. Methods: In this case–control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted. Findings: Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91–1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89–5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7–3), autoimmune thyroiditis (OR 1.26, CI 0.57–2.81), systemic lupus erythematosus (OR 1.21, CI 0.48–3.02), Crohn's disease (OR 1.19, CI 0.75–1.9), and Sjogren's syndrome (OR 1.18, CI 0.65–2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies. Interpretation: We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited. Funding: There was no funding source for this study.

This paper proposes a bivariate three-point interpolation method based on coordinate transformation. The transformation significantly improves computational efficiency by converting radial sampling points into interpolation nodes, while enabling high-precision computation of coordinates and normal vectors for any surface point. Numerical experiments validate the effectiveness of the bivariate three-point interpolation method based on coordinate transformation. Although its accuracy is slightly lower than that of the NURBS surface method, it still meets the requirement for high precision. In particular, the proposed method drastically reduces the computation time by more than 50% compared to the NURBS surface method. In addition, it seamlessly computes coordinates and normal vectors for any surface point. It is significantly helpful for the improvement of computational efficiency in engineering for the measurement and evaluation of aircraft radomes.

Olfaction plays an important role in the survival and reproduction of various organisms. Aside from being a nutrient, in many fish species, amino acids also function as attractants to induce feeding behaviors. As the herbivorous fish, blunt snout bream (Megalobrama amblycephala) commonly consumes an aquatic plant, Hydrilla verticillata. Here, we studied the effect of food odors on the feeding behavior of blunt snout bream using a mixture of amino acids and H. verticillata extract. The behavioral and electro-olfactogram tests demonstrated that the mixture of amino acids and H. verticillata extract induced an attractive reaction and olfactory response in blunt snout bream, respectively. Through Western blotting and immunohistochemical analyses, we confirmed that ciliated and microvillus neurons are distributed on the olfactory placode. The results of phospho-extracellular regulated protein kinases (pERK) showed that a large number of microvillus and ciliated neurons were activated under the stimulation of 10−5 mol/L amino acid mixture and 0.005× H. verticillata extract. The calcium signal imagery demonstrated that the nerve signals of the olfactory bulb were activated by the food odors. The quantitative real-time PCR (qPCR) analysis revealed significant changes in the expression of representative olfactory receptor genes in the olfactory bulb and brain of blunt snout bream upon stimulation with food odor. Collectively, these results provided evidence and preliminary explanations for the mediating role of olfaction in the feeding behavior of fish.

Summary: Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single-nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-dependent gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. Short hairpin RNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of muscle atrophy associated with cancer cachexia and highlight potential therapeutic targets for this disorder.

Five Cr-containing refractory high-entropy alloy (RHEA) coatings were prepared by magnetron sputtering technology and then exposed to static lead–bismuth eutectic to investigate their oxidation resistances at 550–650 °C. The obtained TiNbCrMoV coating had a BCC crystalline structure, while the others were amorphous. The TiNbCrMoV coating exhibited the best corrosion resistance, followed by TiNbZrCrV and CrNbZrMoV coatings, and finally TiCrZrMoV and TiNbZrMoCr coatings. The excellent corrosion resistance of TiNbCrMoV coating was mainly attributed to the presence of grain boundaries which provided the diffusion channels of atoms, thus forming a protective oxide layer. Possible mechanisms were proposed to help understand the corrosion behaviors of these RHEA coatings.

This study investigated the impact of Human Papillomavirus (HPV) on inflammation and growth in oral epithelial cells, with a focus on the role of Interleukin-37 (IL37). Oral epithelial cells, including HOEC and HSC-3 cells, were employed in the research. The results revealed that HPV significantly induced inflammation in both types of oral epithelial cells, concurrently promoting cell growth and inhibiting apoptosis. IL37, a cytokine, was found to mitigate HPV-induced inflammation in oral epithelial cells. Moreover, IL37 counteracted HPV's effects on apoptosis and cell viability in oral epithelial cells. The study also identified a reduction in autophagy in HPV-infected oral epithelial cells, a phenomenon alleviated by IL37. Furthermore, chemical inhibition of autophagy was observed to attenuate HPV-induced inflammation and growth in oral epithelial cells. These findings contribute valuable insights into the pathogenesis of inflammation in oral epithelial cells associated with HPV and oral cancers, offering potential avenues for novel therapeutic strategies.