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Abstract Background Sjögren’s syndrome is a common autoimmune disease that can involve the nervous system, but rarely both the central and peripheral. Long-term use of high-dose corticosteroids and immunosuppressants are the main risk factors for Cryptococcus infection in patients with Sjögren’s syndrome, of which pulmonary infection is the most common, while multiple bone infections are rare. Case presentation A 46-year-old Chinese woman with a 2-year history of Sjögren’s syndrome presented to our hospital with numbness of limbs, shortness of breath, and weakness. Blood immunochemistry showed that antinuclear antibody (1:640), anti-Sjögren’s syndrome-A antibodies, and anti-centromere antibodies were strongly positive. Cranial magnetic resonance imaging revealed multiple demyelinating lesions in the white matter of bilateral cerebral hemispheres. Electromyography indicated serious peripheral nerve injury, especially in lower limbs. Computed tomography scan of lumbar vertebral displayed multiple high-density shadows, and the corresponding vertebrae on magnetic resonance imaging showed abnormal low signal intensity on T1 and T2 sequences. Positron emission tomography–computed tomography showed multiple lesions with high 18F-fluorodeoxyglucose uptake in lung and vertebral bodies. Both lung and bone biopsies suggested Cryptococcus infection, with the diagnosis of Sjögren’s syndrome with nervous system injury combined pulmonary and osseous cryptococcosis. She took a reduced dose of prednisone about 10 mg/day, terminated mycophenolate mofetil, and began to take immunoglobulin of 0.4 g/kg/day intravenously for 5 days, fluconazole (400 mg/day) for 6 months. Within 3 weeks, her chest radiography showed a marked improvement, and 3 months later, the pulmonary lesions disappeared on her computed tomography scan. Conclusions This case exhibits an extremely rare condition of neural involvement in Sjögren’s syndrome combined with pulmonary and osseous cryptococcosis. This report also highlights the crucial role of detailed clinical examination, serologic markers, and biopsy in avoiding misdiagnosis. Currently, there is no guideline for this situation; in this case, we controlled the disease successfully with antifungal drugs and adequate gamma globulin, followed by an appropriate dose of corticosteroids.

The application of large language models in process specifications is an effective approach to addressing the issue of inaccurate process knowledge queries. At present, the domain model construction methods through domain knowledge graph embedding or fine-tuning with instruction data are not effective. The difficulty lies in the fact that the process knowledge in the process specifications involves relationships between multiple process elements, which is highly complex. The data are sparse because the standards are only used through citation. The high complexity of process knowledge and sparse data limit the model’s ability to learn process domain concepts, the relationships between concepts and attributes, the relationships between concepts, the relationships between multiple concepts, and reference-based knowledge. To address this difficulty, this paper proposes a large language model knowledge injection method for process specification texts. According to the characteristics of process specification data, this paper designs knowledge injection data including auxiliary sentence identification task, concept-chapter generation task, chapter continuation task and chapter-summary generation task. The model is fine-tuned through supervised learning by combining question-answer pair data to inject domain concepts, attributes, relationships between multiple concepts, and reference knowledge into the model. Experimental results show that the model trained with knowledge injection data and question-answer pair data improves ACC (accuracy) by 7.3 percentage points, ROUGE-L by 7.4 percentage points, and BLEU-4 by 6.2 percentage points compared with the model trained only with question-answer pair data, indicating the effectiveness of the proposed knowledge injection method.

In response to thermal runaway (TR) of electric vehicles, recent attention has been focused on mitigation strategies such as efficient heat dredging in battery thermal management. Thermal management with particular focus on battery cooling has been becoming increasingly significant. TR usually happened when an electric vehicle is unpowered and charged. In this state, traditional active battery cooling schemes are disabled, which can easily lead to dangerous incidents due to loss of cooling ability, and advanced passive cooling strategies are therefore gaining importance. Herein, we developed an enhanced thermal radiation material, consisting of ∼1 ​μm thick multilayered nano-sheet graphene film coated upon the heat dissipation surface, thereby enhancing thermal radiation in the nanoscale. The surface was characterized on the nanoscale, and tested in a battery-cooling scenario. We found that the graphene-based coating's spectral emissivity is between 91 ​% and 95 ​% in the mid-infrared region, and thermal experiments consequently illustrated that graphene-based radiative cooling yielded up to 15.1 ​% temperature reduction when compared to the uncoated analogue. Using the novel graphene surface to augment a heat pipe, the temperature reduction can be further enlarged to 25.6 ​%. The new material may contribute to transportation safety, global warming mitigation and carbon neutralization.

Abstract Background Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. Methods The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. Results In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: − 0.43, − 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: − 0.61, − 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: − 0.69, − 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. Conclusions This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission. Graphical Abstract

Abstract Background The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. Methods The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. Results In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37–13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38–0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01–0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92–7.59) and 13.63 (95% CI: 9.44–18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73–2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09–0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00–0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32–8.32) and 10.00 (95% CI: 6.09–14.05), respectively. Conclusions The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection. Graphical Abstract

Abstract Subarachnoid hemorrhage (SAH) is one of the most severe type of cerebral strokes, which can cause multiple cellular changes in the brain leading to neuronal injury and neurological deficits. Specifically, SAH can impair adult neurogenesis in the hippocampal dentate gyrus, thus may affecting poststroke neurological and cognitive recovery. Here, we identified a non-canonical role of milk fat globule epidermal growth factor 8 (MFGE8) in rat brain after experimental SAH, involving a stimulation on adult hippocampal neurogenesis(AHN). Experimental SAH was induced in Sprague-Dawley rats via endovascular perforation, with the in vivo effect of MFGE8 evaluated via the application of recombinant human MFGE8 (rhMFGE8) along with pharmacological interventions, as determined by hemorrhagic grading, neurobehavioral test, and histological and biochemical analyses of neurogenesis related markers. Results: Levels of the endogenous hippocampal MFGE8 protein, integrin-β3 and protein kinase B (p-Akt) were elevated in the SAH relative to control groups, while that of hippocalcin (HPCA) and cyclin D1 showed the opposite change. Intraventricular rhMGFE8 infusion reversed the decrease in doublecortin (DCX) immature neurons in the DG after SAH, along with improved the short/long term neurobehavioral scores. rhMGFE8 treatment elevated the levels of phosphatidylinositol 3-kinase (PI3K), p-Akt, mammalian target of rapamycin (mTOR), CyclinD1, HPCA and DCX in hippocampal lysates, but not that of integrin β3 and Akt, at 24 hr after SAH. Treatment of integrin β3 siRNA, the PI3K selective inhibitor ly294002 or Akt selective inhibitor MK2206 abolished the effects of rhMGFE8 after SAH. In conclusion, MFGE8 is upregulated in the hippocampus in adult rats with reduced granule cell genesis. rhMFGE8 administration can rescue this impaired adult neurogenesis and improve neurobehavioral recovery. Mechanistically, the effect of MFGE8 on hippocampal adult neurogenesis is mediated by the activation of integrin β3/Akt pathway. These findings suggest that exogenous MFGE8 may be of potential therapeutic value in SAH management. Graphical abstract and proposed pathway of rhMFGE8 administration attenuate hippocampal injury by improving neurogenesis in SAH models. SAH caused hippocampal injury and neurogenesis interruption. Administered exogenous MFGE8, recombinant human MFGE8(rhMFGE8), could ameliorate hippocampal injury and improve neurological functions after SAH. Mechanistically, MFGE8 bind to the receptor integrin β3, which activated the PI3K/Akt pathway to increase the mTOR expression, and further promote the expression of cyclin D1, HPCA and DCX. rhMFGE8 could attenuated hippocampal injury by improving neurogenesis after SAH, however, know down integrin β3 or pharmacological inhibited PI3K/Akt by ly294002 or MK2206 reversed the neuro-protective effect of rhMFGE8.

Abstract The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

Abstract Purpose Few studies have focused on the risk factors leading to postoperative blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures (PHFs) in the elderly. Therefore, we designed this study to explore potential risk factors of blood transfusion after ORIF for PHFs. We have also established a nomogram model to integrate and quantify our research results and give feedback. Methods In this study, we retrospectively analyzed the clinical data of elderly PHF patients undergoing ORIF from January 2020 to December 2021. We have established a multivariate regression model and nomograph. The prediction performance and consistency of the model were evaluated by the consistency coefficient and calibration curve, respectively. Results 162 patients met our inclusion criteria and were included in the final study. The following factors are related to the increased risk of transfusion after ORIF: time to surgery, fibrinogen levels, intraoperative blood loss, and surgical duration. Conclusions Our patient-specific transfusion risk calculator uses a robust multivariable model to predict transfusion risk.The resulting nomogram can be used as a screening tool to identify patients with high transfusion risk and provide necessary interventions for these patients (such as preoperative red blood cell mobilization, intraoperative autologous blood transfusion, etc.).

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ?at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P

Purpose: This study aimed to investigate the effectiveness and safety of endovascular revascularisation of intracranial artery occlusion and stenosis in moyamoya disease using stent angioplasty. Materials and methods: We recruited 12 patients (8 women and 4 men) with occlusion and stenosis of intracranial arteries in the context of moyamoya disease who underwent endovascular stent angioplasty. Clinical data, baseline conditions, lesion location, treatment outcomes, periprocedural complications, and follow-up outcomes were analysed. Results: The occlusion was located at the M1 segment of the middle cerebral artery in 8 patients, at both the M1 and A2 segments in one patient, and at the C7 segment of the internal carotid artery in 3. Thirteen stents were deployed at the occlusion site, including the low-profile visualized intraluminal support (LVIS) device in 8 patients, an LVIS device and a Solitaire AB stent in one, and a Leo stent in 3, with a success rate of 100% and no intraprocedural complications. Plain CT imaging after stenting revealed leakage of contrast agent, which disappeared on the second day, resulting in no clinical symptoms or neurological sequelae. Follow-up angiography studies were performed in all patients for 6–12 months (mean, 8.8). Slight asymptomatic in-stent stenosis was observed in 2 patients (16.7%), and no neurological deficits were observed in the other patients. All preoperative ischaemic symptoms completely disappeared at follow-up. Conclusion: Stent angioplasty is a safe and effective treatment for occlusion and stenosis of intracranial arteries in moyamoya disease. Resumen: Objetivos: Evaluamos la eficacia y la seguridad de la revascularización endovascular de oclusiones y estenosis de arterias intracraneales mediante angioplastia con stent en pacientes con enfermedad de moyamoya. Materiales y métodos: Incluimos a 12 pacientes (8 mujeres y 4 hombres) con oclusiones y estenosis de arterias intracraneales en el contexto de enfermedad de moyamoya que se sometieron a angioplastia con stent. Recogimos datos clínicos e información sobre enfermedades existentes, localización de la lesión, resultados terapéuticos, complicaciones periprocedimiento y resultados de seguimiento. Resultados: La oclusión afectaba al segmento M1 de la arteria cerebral media en 8 pacientes, a los segmentos M1 y A2 en un paciente, y al segmento C7 de la arteria carótida interna en los 3 restantes. Se colocaron 13 stents en el lugar de la oclusión: stents LVIS en 8 pacientes, un stent LVIS y un stent Solitaire AB en un paciente y stents Leo en 3 pacientes. La tasa de éxito fue del 100%, sin complicaciones durante el procedimiento. Una TC tras el procedimiento detectó fugas del medio de contraste, que desaparecieron al segundo día y no provocaron síntomas ni secuelas neurológicas. Se realizó un seguimiento de todos los pacientes con angiografía durante 6-12 meses (media: 8,8 meses). Dos pacientes (16,7%) presentaron una ligera reestenosis intrastent asintomática; el resto de los pacientes no presentaron déficits neurológicos. Todos los síntomas isquémicos previos desaparecieron durante el seguimiento. Conclusiones: La angioplastia con stent es un tratamiento eficaz y seguro de las oclusiones y estenosis de arterias intracraneales en pacientes con enfermedad de moyamoya.

Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKOPrrx1-cre mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database. Signature component Lgals3 encoding galectin-3 was increased in Tsc2-deficient cells and serum of Tsc2cKOPrrx1-cre mice. Galectin-3 was increased in TSC-related skin tumors, angiomyolipomas, and lymphangioleiomyomatosis with serum levels in patients with lymphangioleiomyomatosis correlating with impaired lung function and angiomyolipoma presence. Our results demonstrate Tsc2-deficient mesenchymal progenitors cause aberrant morphogenic signals, and identify an expression signature including Lgals3 relevant for human disease of TSC1/TSC2 inactivation and mTORC1 hyperactivity.

Nonlinear dielectric metasurfaces provide a promising approach to control and manipulate frequency conversion optical processes at the nanoscale, thus facilitating both advances in fundamental research and the development of new practical applications in photonics, lasing, and sensing. Here, we employ symmetry-broken metasurfaces made of centrosymmetric amorphous silicon for resonantly enhanced second- and third-order nonlinear optical response. Exploiting the rich physics of optical quasi-bound states in the continuum and guided mode resonances, we comprehensively study through rigorous numerical calculations the relative contribution of surface and bulk effects to second-harmonic generation (SHG) and the bulk contribution to third-harmonic generation (THG) from the meta-atoms. Next, we experimentally achieve optical resonances with high quality factors, which greatly boosts light-matter interaction, resulting in about 550 times SHG enhancement and nearly 5000-fold increase of THG. A good agreement between theoretical predictions and experimental measurements is observed. To gain deeper insights into the physics of the investigated nonlinear optical processes, we further numerically study the relation between nonlinear emission and the structural asymmetry of the metasurface and reveal that the generated harmonic signals arising from linear sharp resonances are highly dependent on the asymmetry of the meta-atoms. Our work suggests a fruitful strategy to enhance the harmonic generation and effectively control different orders of harmonics in all-dielectric metasurfaces, enabling the development of efficient active photonic nanodevices.

Objective: To evaluate the anti-allergic effect of boeravinone B against ovalbumin-induced allergic rhinitis in mice and explore its possible mechanism. Methods: For the induction of allergic rhinitis, mice were intraperitoneally sensitized and intranasally challenged with ovalbumin, as well as orally received various concentrations of boeravinone B. Nasal mucosal inflammation, and the levels of nitric oxide, β-hexosaminidase, IFN-γ, LTC-4, myeloperoxidase, Nrf2, HO-1, GATA-3, ROR-γ, T-bet, antioxidant parameters, and allergen-specific cytokines were assessed. Results: Boeravinone B markedly reduced ovalbumin-induced increase in the number of episodes of nasal sneezing, rubbing, and discharge, as well as the levels of IgE, IgG1, and β-hexosaminidase (P

This article reports a case of acute myelomonocytic leukemia (AML-M4, CBFB gene positive) with lower limb microthrombus formation after haploidentical hematopoietic stem cell transplantation, and summarizes the experience of diagnosis and treatment. The patient received achieved complete remission (CR) after routine chemotherapy, but relapsed 2 years later and underwent a haploidentical hematopoietic stem cell transplantation. During routine treatment after transplantation, the patient’s coagulation related indicators, including D-dimer (D-D), antithrombin Ⅲ (AT-Ⅲ), von Willebrand factor (vWF), fibrinogen degradation products (FDP) and fibrin monomer (FM), were dynamically observed. The patient experienced jaundice and elevated transaminases around 100 days after transplantation, and underwent plasma exchange treatment three times through the right lower limb femoral vein catheterization. After removing the venous catheter for one week, there was left ankle concavea pitting edema of the left ankle. Vascular ultrasound examination indicated the formation of microthrombus in the superficial venous plexus of the gastrocnemius muscle in the left lower limb. D-D, vWF, FDP, FM and other indicators were increased, while AT-Ⅲ levels was decreased. After 2 weeks of oral administration of 5 mg/d berritol for antithrombotic treatment, the above coagulation indicators gradually returned to normal, and the left lower limb intermuscular venous plexus thrombosis and limb swelling disappeared. Therefore, dynamic monitoring of coagulation indicators, such as D-D, AT-Ⅲ, vWF, FDP, and FM may serve as diagnostic indicators for predict transplant related microthrombus and hypercoagulable status, providing an experimental basis for effective anticoagulant treatment in clinical practice.

Aiming at the problem of uncertainty and complexity of battlefield situation, which leads to the poor accuracy of risk prediction in the process of research and judgment, it is proposed to build a situation-risk model and construct the risk possibility distribution in order to realize the accurate prediction of risk. Firstly, the risk prediction index system is established from the enemy situation, our situation and the battlefield environment situation research and judgment content; secondly, the role of situation information on the risk is analyzed, and the risk model such as exponential, Z-type, tangent and so on is constructed and the risk value interval is calculated; then, based on the fuzzy function constructing method in the possibility theory, and relying on the weighting difference and uncertainty measurement, the risk possibility distribution is constructed within the risk value interval. Finally, an example of a defense mission is used to verify the feasibility and reasonableness of the proposed method by combining the expert system and cloud modeling methods in an experiment. The results show that the proposed method can fully take into account the uncertainty of situational information in risk prediction, which provides an important basis for subsequent planning decision-making.

To study the relationships between C4 enzyme activities and yield, C4 enzyme activities (phosphoenolpyruvate carboxylase (PEPCase), NADP-malate dehydrogenase (NADP-MDH), NADP-malic enzyme (NADP-ME), and pyruvate phosphate dikinase (PPDK)) in different organs of ten soybean cultivars with different yields were measured at different growth stages in China. The result showed that four enzyme activities in C4 pathway were obviously different among cultivars, especially PPDK activity was not detected in the leaves of Dongnong 1567 and Dongnong 1068 and the young leaves of Gongjiao 9107-1 and Dongnong 97–172, but there were weak activities in pod coats. The order of C4 enzyme activities is young leaves < old leaves < pod coats. The correlation coefficients between PEPCase activity and yield and between NADP-MDH activity at blooming stage and yield were 0.6979 and 0.6565, respectively, and both reached the significant level (5%), and PEPCase activity kept significant positive correlation with plant photosynthetic rate. There was a negative correlation between NADP-ME activity and yield, and no correlation was found between PPDK activity and yield.

Soyasaponins are valuable compounds in certain drugs, industry, food additives and surfactants. Selecting cultivars with higher-soyasaponin content along with agronomic traits is a main goal for many soybean breeders. The aim of the present study was to identify the quantitative trait loci (QTLs) associated with total soyasaponin content through a F2 population, which was derived from a cross between Ha 91016 (higher soyasaponin content cultivar, 16.8 mg g−1) and N98-9445A (lower soyasaponin content, only 5.7 mg g−1). A genetic linkage map including a total of 162 simple sequence repeat markers was constructed, which covered the total length 2 735.5 cM, and the average distance between markers was 16.96 cM. Two QTLs associated with total soyasaponin content were identified. One, qSAP_1 (located in sat_044-satt102 of linkage group (LG) K), could explain 12.6% of phenotypic variance. The other, qSAP_2, was located between satt368 and sat_413 of LG D1a, which could explain 15.8% of phenotypic variance. It was concluded that the two QTLs would have some potential value for marker-assisted selection for high-soyasaponin content breeding in soybeans.

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues and regulates obesity-related diseases; however, the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet-induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced the expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein one (UCP1), and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C-specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1, and mitochondrial complex expression. Our findings reveal that NPR-C deficiency enhances mitochondrial function and energy expenditure in white adipose tissue, contributing to improved metabolic health and resistance to obesity.

Effective exploration of the pattern dynamic behaviors of reaction–diffusion models is a popular but difficult topic. The Schnakenberg model is a famous reaction–diffusion system that has been widely used in many fields, such as physics, chemistry, and biology. Herein, we explore the stability, Turing instability, and weakly non-linear analysis of the Schnakenberg model; further, the pattern dynamics of the fractional-in-space Schnakenberg model was simulated numerically based on the Fourier spectral method. The patterns under different parameters, initial conditions, and perturbations are shown, including the target, bar, and dot patterns. It was found that the pattern not only splits and spreads from the bar to spot pattern but also forms a bar pattern from the broken connections of the dot pattern. The effects of the fractional Laplacian operator on the pattern are also shown. In most cases, the diffusion rate of the fractional model was higher than that of the integer model. By comparing with different methods in literature, it was found that the simulated patterns were consistent with the results obtained with other numerical methods in literature, indicating that the Fourier spectral method can be used to effectively explore the dynamic behaviors of the fractional Schnakenberg model. Some novel pattern dynamics behaviors of the fractional-in-space Schnakenberg model are also demonstrated.

Alzheimer's disease (AD) is the most common global dementia and is universally fatal. Most late-stage AD disease-modifying therapies are intravenous and target amyloid beta (Aβ), with only modest effects on disease progression: there remains a high unmet need for convenient, safe, and effective therapeutics. Senescent cells (SC) and the senescence-associated secretory phenotype (SASP) drive AD pathology and increase with AD severity. Preclinical senolytic studies have shown improvements in neuroinflammation, tau, Aβ, and CNS damage; most were conducted in transgenic rodent models with uncertain human translational relevance. In this study, aged cynomolgus monkeys had significant elevation of biomarkers of senescence, SASP, and neurological damage. Intermittent treatment with the senolytic navitoclax induced modest reversible thrombocytopenia; no serious drug-related toxicity was noted. Navitoclax reduced several senescence and SASP biomarkers, with CSF concentrations sufficient for senolysis. Finally, navitoclax reduced TSPO-PET frontal cortex binding and showed trends of improvement in CSF biomarkers of neuroinflammation, neuronal damage, and synaptic dysfunction. Overall, navitoclax administration was safe and well tolerated in aged monkeys, inducing trends of biomarker changes relevant to human neurodegenerative disease.

Summary: Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30–70 years with an office blood pressure (BP) of

Due to the complex structures associated with neutron resonance cross sections, their accurate evaluation has received considerable attention in the field of nuclear data research. The traditional R-matrix method still faces some difficulties in evaluating the neutron resonance data, especially in briefly reproducing the high-frequency oscillating cross sections. Recently, the applications of machine learning methods in nuclear physics have been expanding. In this paper, a novel Phase Shift Deep Neural Network (PSDNN) method, which not only overcomes the limitations of other machine learning methods in fitting the high-frequency oscillating data, but also is more concise than the R-matrix method, is developed to reproduce the neutron resonance cross sections. The results show that PSDNN method can simultaneously reproduce the low and high-frequency oscillating cross sections for the 235U(n,f) reaction with high accuracy and efficiency. Moreover, from an algorithmic point of view, the PSDNN method lays a solid foundation for further fine-grained processing of experimental data and extraction of critical neutron resonance parameters, opening up new possibilities for practical applications in nuclear data research.

The dynamic temperature data of a transformer can be utilized to accurately assess its load capability and operational longevity. This paper presents a study on the temperature rise characteristics of hot-spots in dry-type transformer windings and develops a extrapolative computational model based on various load rates, utilizing the results of transformer temperature rise tests. Firstly, the dynamic temperature rise characteristics of B-phase low-voltage (LV) winding and high-voltage (HV) winding hot-spot, along with its correlation calculation model with varying load rates, were determined based on the results of temperature rise tests. Subsequently, an extrapolative computational model for the temperature rise of the winding hot-spot, utilizing a three-section continuous load application approach, was proposed employing the lumped parameter method. The validity of this model was confirmed through verification. Lastly, a temperature rise test was conducted on another dry-type transformer to validate the universality of the model. Finally, a different dry-type transformer is chosen, and a temperature rise test is conducted to confirm the general applicability of the model. The results indicate that the calculation model for the hot-spot temperature rise of the winding under three consecutive loads is associated with the dynamic temperature rise pattern of the hot-spot of the winding between the temperature rise test with a small load rate and the temperature rise test with a large load rate. The maximum deviation between the hot-spot temperature rise test of the winding of SCB14-800/10-NX2 transformer and the results of the steady-state temperature rise value calculation is only 1.3 K, with a maximum error of the time constant value of the temperature rise being only 0.05 h. Similarly, the maximum deviation of the steady-state temperature rise value obtained from the hot-spot temperature rise test and the extrapolative computation of SCB-1250kVA/10 kV transformer winding is only 2.03 K, with a maximum error of the temperature rise time constant value being only 0.09 h. The extrapolative computational model proposed in this study conducts the temperature rise test under a small load rate instead of a large load rate, addressing the industry challenge of the challenging implementation of transformer on-site temperature rise tests and high power loss. This approach enhances inspection efficiency.

General practitioners (GPs) play an important role in diabetes care in primary care as the "gatekeepers" of population health. The management of diabetes can slow its progression, reduce complications and improve patient outcomes, which requires effective communication and collaboration between patients and their doctors. GPs with good communication skills can help to build long-term care relationships with diabetes patients and help them develop effective self-management skills. This paper summarizes the design and development of diabetes communication skills training for GPs guided by research team with multiple theoretical frameworks, including evidence-based findings from systematic review, experiences and ideas of diabetes patients communicating with GPs based on qualitative studies, prioritization of training content for patient-doctor communication in GPs captured by mixed-methods research, in order to provide new ideas for high-quality diabetes management in primary care and inform the design of training programmes for GPs based on evidence and medical education frameworks.

Abstract Background The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. Methods A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein–Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. Results A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value 1.5 or HR/N

Objective To investigate the effect of cisplatin treatment on the transcriptional level of human liver cancer cells by conducting transcriptome sequencing analysis after treating human liver cancer cell lines with different concentrations of cisplatin (CDDP). Methods Liver cancer cell lines HepG2 and Huh7 were incubated with cisplatin at different final concentrations of 0,20,50,100 and 200 μmol/L. After 12 hours, cell viability, immunofluorescence and RNA-sequencing(RNA-seq) were performed. Differential gene expression analysis (DEG), KEGG pathway analysis, and protein-protein interaction network analysis were conducted. Results Cisplatin decreased cell viability and increased DNA damage in HepG2,Huh7 cells. Among the genes regulated after cisplatin treatment at different concentrations, 59 genes were commonly up-regulated in both HepG2 and Huh7 cells, while 81 genes were commonly down-regulated. The commonly upregulated genes were mainly enriched in cancer initiation and progression pathways.The 81 commonly down-regulated genes were mainly enriched in Rap1 signaling pathway, Ras signaling pathway, signaling pathways regulating pluripotency of stem cells, axon guidance, and cell adhesion-related pathways. Survival analysis of key nodes in the protein-protein interaction network of commonly upregulated and downregulated genes revealed a significant correlation between high expression of Jun proto-oncogene, AP-1 transcription factor subunit (JUN) and prolonged patient survival and a significant correlation between low expression of growth arrest and DNA damage inducible alpha (GADD45A) and prolonged patient survival. Conclusions The study revealed common transcriptional changes in liver cancer cells under cisplatin treatment. Differential expression of JUN and GADD45A is a potential core mechanism to explain drug resistance. This conclusion provides some important prognostic indicators for clinical treatment.

Abstract Background The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. Methods Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell–cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. Results Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. Conclusions This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

Abstract Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis.

Abstract Background Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. Methods In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. Results In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was − 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and − 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of − 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were − 1.47 (p = 0.18) in 24-h diastolic BP, − 2.86 (p = 0.13) and − 2.74 (p = 0.03) in daytime systolic and diastolic BP, and − 0.45 (p = 0.82) and − 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). Conclusions The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. Trial registration ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Background & Aims: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. Methods: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. Results: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. Conclusions: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.

Medical radioactive isotopes can be used for diagnosis, treatment of diseases, and production of radiopharmaceuticals. With the attention of the country and the desire of the people, the field of medical radioactive isotope production will soon enter a period of rapid development. This article summarizes the production methods of medical radioactive isotopes and divides them into three categories: reactor, accelerator, and other methods. It focuses on the preparation methods and development status of medical isotopes such as 99Mo, 125I, 131I, 177Lu, 89Sr, 18F, 68Ga, and 225Ac. Combining with the "Medium-to-Long-Term Development Plan for Medical Isotopes (2021-2035)" jointly published by eight ministries and commissions in 2021, this article provides a certain degree of summary of the current situation of domestic radioactive medical isotopes. It can provide researchers with development ideas for a period of time in the future and propose certain development trends and prospects based on the current development situation.

Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

This study optimized a gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS) method for the determination of 21 persistent organic pollutants (POPs) in Irtysh River water, including 14 organochlorines (OCPs) and 7 polychlorinated biphenyls (PCBs). Factors such as column temperature ramping, selection of qualitative and quantitative ion pairs and collision energy were considered to achieve perfect separation and accurate quantification of all 21 target compounds. The limits of detection (LOD) for PCBs and OCPs ranged from 0.21 to 1.18 ng/L. Applying this method to detect POPs in the Irtysh River revealed concentrations of OCPs ranging from ND to 20.2 ng/L and PCBs from ND to 0.411 ng/L. Source analysis indicated that POPs in the Irtysh River mainly originate from historical industrial and agricultural activities, particularly the deliberate use of pesticides. To ensure ecological safety and human health, expanding the range of target analytes and monitoring periods is necessary. This study provides: • Qualitative and quantitative analysis methods for 7 PCBs and 14 OCPs. • Recoveries achieved ranged between 74.6 to 109 % with RSD less than 15 %. • Analysis of sources, transport pathways, accumulation status, and ecological risks of PCBs and OCPs in the Irtysh River.

AbstractObjectives This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features.Methods A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell’s C-index and a calibration curve.Results The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin 3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration.Conclusions The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Abstract Background To date, carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. Methods A total of 1121 patients from the Liver Cancer Clin‐Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular‐cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. Results ROC curves obtained by combining CA50, CA19‐9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856–0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841–0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853–0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818–0.927, 94.2%, and 64.6%) in the validation cohort. Conclusion The model combining CA50, CA19‐9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Fagopyrum dibotrys, belonging to the family Polygonaceae and genus Fagopyrum, is used in traditional Chinese medicine and is rich in beneficial components, such as flavonoids. As its abundant medicinal value has become increasingly recognized, its excessive development poses a considerable challenge to wild germplasm resources, necessitating artificial cultivation and domestication. Considering these factors, a high-quality genome of F. dibotrys was assembled and the evolutionary relationships within Caryophyllales were compared, based on which 58 individual samples of F. dibotrys were re-sequenced. We found that the samples could be categorized into three purebred populations and regions distributed at distinct elevations. Our varieties were cultivated from the parental populations of the subpopulation in central Yunnan. F. dibotrys is speculated to have originated in the high-altitude Tibetan Plateau region, and that its combination with flavonoids can protect plants against ultraviolet radiation; this infers a subpopulation with a high accumulation of flavonoids. This study assembled a high-quality genome and provided a theoretical foundation for the future introduction, domestication, and development of cultivated varieties of F. dibotrys.

This paper introduces a numerical approach for the fractional-order Rössler chaotic systems and gives error analysis. The effectiveness of the present method is determined by comparing the numerical results of the high-precision difference scheme and predictor-correctors scheme. Some complex dynamical behaviors for the fractional-order Rössler chaotic systems are shown.

In this study, a new fermented food was developed using pineapple by-products and whey protein (2.6%) as raw materials through the co-fermentation of autochthonous lactic acid bacteria and yeast. To better understand the fermentation mechanism and the impact of microorganisms on the entire fermentation system, we tracked the changes in carbohydrate and amino acid profiles, organoleptic quality and microbial community during the fermentation process. Compared with unfermented samples, dietary fiber and free amino acids increased significantly as fermentation proceeded. The fermented samples were significantly lower in astringency and bitterness and significantly higher in sourness, umami and richness. The fermented products were richer in volatile compounds with floral, cheesy, fruity and other flavors. Relevant analyses showed that the core microbial community was highly correlated with the quality attributes of the fermented products. Microorganisms such as Lactococcus, Weissella, Hanseniaspora, Saccharomyces and Lachancea contributed significantly to the fermented products.

Abstract Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field. Graphical abstract

Abstract Background Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. Methods A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. Results Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P

Background Acute hypoxic injury caused by acute altitude exposure is manifested by different degrees of clinical symptoms, some of which may develop into acute mountain sickness (AMS). However, the current prevention and treatment methods are limited and there is a lack of safe and effective methods to prevent and reduce the severity. Objective To investigate the efficacy and safety of intermittent hypoxic (IH) training in preventing acute hypoxic injury by simulating hypoxic environment at an altitude of 4 400 meters. Methods A total of 40 subjects were recruited by public recruitment in Beijing Xiaotangshan Hospital from 2022-08-01 to 10-31 and randomly divided into the IH group (experimental group, n=20) and sham training group (control group, n=20). The experimental group received the IH exposure intervention with the total duration of 55 min twice a day for 5 d, including 10 min of low oxygen (oxygen concentration of 13%, simulated altitude of 3 800 m), 5 min of normoxia (oxygen concentration of 21%). The control group received the simultaneous long normoxia intervention. On the first day after the IH intervention training, the subjects entered into the simulated high-altitude hypoxia environment for 6 h, and the oxygen concentration was set at 12% (equivalent to the altitude of 4 400 m). The Lake Louise Scale (LLS) was used to assess the severity of AMS. Peripheral oxygen saturation (SpO2), cerebral oxygen saturation (ScO2) and intracranial pressure (ICP) were collected at baseline, before and 6 h after the simulated high-altitude hypoxia environment. Results After 6 h of acute high-altitude hypoxia environment simulation, the incidence of AMS and LLS in the experimental group were significantly lower than those in the control group (P

Abstract Tunneling spectroscopy is widely used to examine the subgap spectra in semiconductor-superconductor nanostructures when searching for Majorana zero modes (MZMs). Typically, semiconductor sections controlled by local gates at the ends of hybrids serve as tunnel barriers. Besides detecting states only at the hybrid ends, such gate-defined tunnel probes can cause the formation of non-topological subgap states that mimic MZMs. Here, we develop an alternative type of tunnel probes to overcome these limitations. After the growth of an InSb-Al hybrid nanowire, a precisely controlled in-situ oxidation of the Al shell is performed to yield a nm-thick AlOx layer. In such thin isolating layer, tunnel probes can be arbitrarily defined at any position along the hybrid nanowire by shadow-wall angle-deposition of metallic leads. In this work, we make multiple tunnel probes along single nanowire hybrids and successfully identify Andreev bound states (ABSs) of various spatial extension residing along the hybrids.

Numbers of vertebrae is an important economic trait associated with body size and meat productivity in animals. However, the genetic basis of vertebrae number in donkey remains to be well understood. The aim of this study was to identify candidate genes affecting the number of thoracic (TVn) and the number of lumbar vertebrae (LVn) in Dezhou donkey. A genome-wide association study was conducted using whole genome sequence data imputed from low-coverage genome sequencing. For TVn, we identified 38 genome-wide significant and 64 suggestive SNPs, which relate to 7 genes (NLGN1, DCC, SLC26A7, TOX, WNT7A, LOC123286078, and LOC123280142). For LVn, we identified 9 genome-wide significant and 38 suggestive SNPs, which relate to 8 genes (GABBR2, FBXO4, LOC123277146, LOC123277359, BMP7, B3GAT1, EML2, and LRP5). The genes involve in the Wnt and TGF-β signaling pathways and may play an important role in embryonic development or bone formation and could be good candidate genes for TVn and LVn.

This paper studies the single-machine scheduling problem with truncated learning effect, time-dependent processing time, and past-sequence-dependent delivery time. The delivery time is the time that the job is delivered to the customer after processing is complete. The goal is to determine an optimal job schedule to minimize the total weighted completion time and maximum tardiness. In order to solve the general situation of the problem, we propose a branch-and-bound algorithm and other heuristic algorithms. Computational experiments also prove the effectiveness of the given algorithms.