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Inhibitory compounds generated from lignocellulose pretreatment would inhibit Poly (malic acid) (PMA) production by Aureobasidium pullulans, but the tolerance mechanism of A. pullulans to lignocellulosic inhibitor is poorly understood. In this study, the cellular response of A. pullulans to lignocellulosic inhibitor stress was studied. Among the three groups of inhibitors (furans, weak acids and phenolic aldehydes), phenolic aldehyde was the dominant inhibitor for PMA production. Phenolic aldehyde was mainly converted into phenolic alcohol by A. pullulans, and phenolic alcohol also exhibited severe inhibition on PMA production. Furthermore, the effect of detoxification methods on inhibitor-removal and PMA fermentation was investigated, both CaCO3 and overliming presented poor detoxification effect, whereas resin H103 could remove both furan derivatives and phenolic compounds efficiently, thereby producing 26.27 g/L of PMA with a yield of 0.30 g/g in batch fermentation. This study will be beneficial for the development of PMA production from lignocellulosic biomass.

Summary: Memory-augmented neural network (MANN) has received increasing attention as a promising approach to achieve lifelong on-device learning, of which implementation of the explicit memory is vital. Content addressable memory (CAM) has been designed to accelerate the explicit memory by harnessing the in-memory-computing capability. In this work, a CAM cell with quadratic code is proposed, and a 1Mb Flash-based multi-bit CAM chip capable of computing Euclidean (L2) distance is fabricated. Compared with ternary CAM, the latency and energy are significantly reduced by 5.3- and 46.6-fold, respectively, for the MANN on Omniglot dataset. Besides, the recognition accuracy has slight degradation (

BackgroundStarting in 2010, the Chinese government initiated a 10-year syphilis control plan, called the national syphilis control plan (NSCP), to address the emerging threat of syphilis. We aimed to evaluate the effect of the NSCP plan on syphilis control in Jiangsu, China.MethodsThe temporal trends of syphilis incidence, prevalence and rate of condom use were estimated by Joinpoint regression with average annual percent change (APC) and average annual percentage (APPC). A Chi-square test was conducted to analyze the outcomes in different subgroups. ArcGIS was used to analyze the spatiotemporal distribution of syphilis incidence.ResultsGeographically, early and congenital syphilis incidence decreased significantly in all areas of the province during the period of NSCP. Early syphilis incidence decreased from 21.1 to 8.8 (APC: −7.5, 95%CI: −8.6, −6.5, p

Abstract Hematologic malignancies are among the most common cancers, and understanding their incidence and death is crucial for targeting prevention, clinical practice improvement, and research resources appropriately. Here, we investigated detailed information on hematological malignancies for the period 1990–2019 from the Global Burden of Disease study. The age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and the corresponding estimated annual percentage changes (EAPC) were calculated to assess temporal trends in 204 countries and territories over the past 30 years. Globally, incident cases of hematologic malignancies have been increasing since 1990, reaching 1343.85 thousand in 2019, but the ASDR for all types of hematologic malignancies has been declining. The ASDR for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were 4.26, 1.42, 3.19, and 0.34 per 100,000 population in 2019, respectively, with Hodgkin lymphoma showing the most significant decline. However, the trend varies by gender, age, region, and the country’s economic situation. The burden of hematologic malignancies is generally higher in men, and this gender gap decreases after peaking at a given age. The regions with the largest increasing trend in the ASIR of leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were Central Europe, Eastern Europe, East Asia, and Caribbean, respectively. In addition, the proportion of deaths attributed to high body-mass index continued to rise across regions, especially in regions with high socio-demographic indices (SDI). Meanwhile, the burden of leukemia from occupational exposure to benzene and formaldehyde was more widespread in areas with low SDI. Thus, hematologic malignancies remain the leading cause of the global tumor burden, with growing absolute numbers but sharp among several age-standardized measures over the past three decades. The results of the study will inform analysis of trends in the global burden of disease for specific hematologic malignancies and develop appropriate policies for these modifiable risks.

Objective: To compare and analyze the clinical and chest computed tomography (CT) imaging features of COVID-19 patients with different disease courses. Methods: A retrospective analysis was performed for 161 cases with confirmed COVID-19 and positive chest CT lung infections from December 2022 to January 2023 at the fever clinic of Beijing Shijitan Hospital affiliated with Capital Medical University. The patients were divided into two groups based on the time of CT examination:

Objective: This study aimed to investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and chest high-resolution computed tomography (HRCT) findings of coronavirus disease 2019 (COVID-19). Materials and Methods: NLR and chest HRCT findings of 132 patients diagnosed with COVID-19 in the department of infectious diseases of Beijing Shijitan Hospital Capital Medical University from December 1, 2022 to February 1, 2023 were retrospectively analyzed. The patients were divided into two groups with NLR cut-off value of 3.0, and their HRCT characteristics and imaging manifestation patterns were analyzed. For the measurement data of normal distribution, the t-test of continuous variables was used between the groups. The data of non-normal distribution are expressed as median and quartile and compared using Mann-Whitney U test. The counting data are expressed as frequency, and the chi-squared or Fisher's exact test was used for comparison between the groups. P10 and the proportion of lesions >50% were higher in the high NLR group than that in the low NLR group. The high NLR group was prone to mixed density shadow, crazy-paving pattern, mosaic sign, anti-halo sign, subpleural black belt, arcade-like sign than that in the low NLR group. The high NLR group was most likely to have nonspecific interstitial pneumonia-like, organizing pneumonia-like, and diffuse alveolar damage-like patterns than that in the low NLR group. Conclusion: Different NLRs have different manifestations of COVID-19 chest HRCT. The high NLR group is more prone to mixed density shadow, crazy-paving pattern, mosaic sign, anti-halo sign, subpleural black belt, and arcade-like sign, as well as most likely to have radiologic patterns of nonspecific interstitial pneumonia, organizing pneumonia, diffuse alveolar damage.

Purpose: The ASCENT trial demonstrated the efficacy of sacituzumab govitecan for the treatment of advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of receiving sacituzumab govitecan compared with standard of care chemotherapy from the United States payer perspective. Methods: A partitioned survival approach was used to project the disease course of advanced or metastatic TNBC. Two survival modes were applied to analyze two groups of patients. The survival data were gathered from the ASCENT trial. Direct medical costs were derived from the data of Centers for Medicare & Medicaid Services. Utility data was collected from the published literature. The incremental cost-utility ratio (ICUR) was the primary outcome that measured the cost-effectiveness of therapy regimen. One-way sensitivity and probabilistic sensitivity analysis were implemented to explore the uncertainty and validate the stability of results. Results: In the base-case, the ICUR of sacituzumab govitecan versus chemotherapy is $ 778,771.9/QALY and $ 702,281/QALY for full population group and brain metastatic-negative (BMN) group with the setting of classic survival mode. And in the setting of cure survival mode, the ICUR is $ 506,504.5/QALY for the full population group and $ 274,232.0/QALY for BMN population group. One-way sensitivity analyses revealed that the unit cost of sacituzumab govitecan and body weight were key roles that lower the ICUR value. Probabilistic sensitivity analyses also showed that reducing the unit price of sacituzumab govitecan can improve the likelihood of becoming cost-effective. Conclusion: The cost-effectiveness analysis suggested that from a US payer perspective, sacituzumab govitecan at current price is unlikely to be a preferred option for patients with advanced or metastatic TNBC at a threshold of $ 150,000/QALY.

Abstract Chemical warfare agents (CWAs) significantly threaten human peace and global security. Most personal protective equipment (PPE) deployed to prevent exposure to CWAs is generally devoid of self-detoxifying activity. Here we report the spatial rearrangement of metal-organic frameworks (MOFs) into superelastic lamellar-structured aerogels based on a ceramic network-assisted interfacial engineering protocol. The optimized aerogels exhibit efficient adsorption and decomposition performance against CWAs either in liquid or aerosol forms (half-life of 5.29 min, dynamic breakthrough extent of 400 L g−1) due to the preserved MOF structure, van-der-Waals barrier channels, minimized diffusion resistance (~41% reduction), and stability over a thousand compressions. The successful construction of the attractive materials offers fascinating perspectives on the development of field-deployable, real-time detoxifying, and structurally adaptable PPE that could be served as outdoor emergency life-saving devices against CWAs threats. This work also provides a guiding toolbox for incorporating other critical adsorbents into the accessible 3D matrix with enhanced gas transport properties.

The C3 parametric interpolation spline function is presented this paper, which has the similar properties of the classical cubic Hermite interpolation spline with additional flexibility and high approximation rates. Moreover, a group of eighth-degree bases with three parameters is constructed. Then, the interpolation spline function is defined based on the proposed basis functions. And the interpolation error and the technique for determining the optimal interpolation are also given. The results show that when the interpolation conditions remain unchanged, the proposed interpolation spline functions retain C3 continuity, and the shape of the curve can be controlled by the parameters. When the optimal values of parameters are chosen, the interpolation spline function can achieve higher approximation rates.

Abstract Introduction Immune checkpoint inhibitor (ICI)‐based treatment regimens have become the standard of care for first‐line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild‐type non‐small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first‐line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second‐line therapy options. Plinabulin is a selective immunomodulating microtubule‐binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD‐1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance. Methods In this investigator‐initiated, single‐arm, open‐label, phase II trial, metastatic NSCLC patients who acquired resistance to first‐line immunotherapy‐based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m2 D1 and D8, and docetaxel 75 mg/m2 D1 intravenously for a 21‐day cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator‐based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression‐free survival, overall survival, duration of response, and safety. Discussion This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first‐line PD‐1/PD‐L1 inhibitor either as monotherapy or in combination with chemotherapy.

Abstract Background Atherosclerosis (AS) is a chronic inflammatory disease, as a main cause leading to vascular diseases worldwide. Although increasing studies have focused on macrophages in AS, the exact relating mechanism is still largely unclear. Our study aimed to explore the pathogenic role and diagnostic role of macrophage autophagy related genes (MARGs) in AS. Methods All datasets were downloaded from Gene Expression Omnibus database and Human Autophagy Database. The differential expression analysis and cross analysis were performed to identify candidate MARGs. GO and KEGG enrichment analyses were conducted to obtain the functional information. Moreover, we analyzed the correlation between target gene and macrophage polarization in AS. The correlation between target gene and plaque instability, different stages of AS were also analyzed. Results Compared with normal samples, a total of 575 differentially expressed genes (DEGs) were identified in AS samples. A total of 12 overlapped genes were obtained after cross-analysis of the above 575 DEGs and autophagy related genes (ARGs). Then, 10 MARGs were identified in AS samples, which were significantly enriched in 22 KEGG pathways and 61 GO terms. The expression of HSPB8 was significantly down-regulated in atherosclerotic samples compared with normal samples (with largest fold change). Meanwhile, the proportion of M-CSF in low HSPB8 expression AS group was higher than high expression AS group. Furthermore, the expression of HSPB8 was negatively correlated with most inflammatory factors. Conclusion The downregulation of MARG HSPB8 probably involves in the M2 macrophage polarization in AS samples. HSPB8 is a promising diagnostic marker for AS patients.

Abstract Background Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. Methods This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. Results A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt–Jakob disease (13.4%), Alzheimer’s disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P

The conflict of strength and ductility has always been a huge challenge when developing advanced structural materials. The introduction of nano-scaled precipitates into metallic materials through composition design is a well-established method for achieving the strength-ductility balance. Herein, a series of non-equiatomic FeCoNi based medium-entropy alloys (MEAs) with Al and Ti combination addition were prepared by vacuum induction melting, and its phase constitution, microstructural changes and mechanical properties were systemically studied. The microstructure of Al/Ti co-doped alloys are composed of BCC phase + FCC phase + L21 nanoparticles structure, in which the L21 nanoparticles are homogeneously distributed and coherent with matrix. By tailoring Al/Ti ratio, the as-cast Ni0.6CoFe1.6 MEA presents a good strength-ductility combination. Among them, the Al0.2Ti0.1 MEA possesses higher yield strength of 837.7 ± 18.9 MPa and ultimate tensile strength of 1305.4 ± 22.0 MPa, as well as maintains an acceptable failure strain of 12.3 ± 0.7%. The improvement of yield strength is originated from the contributions of the precipitation hardening, grain boundary strengthening, and solid solution strengthening. The present study provides a new avenue to design strong yet ductile MEAs for industrial applications.

Abstract Introduction This study investigated whether programmed death‐ligand 1 (PD‐L1) expression of circulating tumor cells (CTCs) in peripheral blood can serve as a predictive biomarker for immunotherapy efficacy in patients with advanced non‐small‐cell lung cancer (NSCLC). Methods We employed a negative enrichment method to isolate CTCs. We identified PD‐L1 + CTCs as PD‐L1+/4′,6‐diamidino‐2‐phenylindole (DAPI)+/CD45‐circulating tumor cells through an immunofluorescence method. Tumor tissue PD‐L1 expression was determined by immunohistochemical staining. The correlation between CTC PD‐L1 expression and patients' prognostic features was estimated through the Kaplan–Meier method. Results CTCs released a higher detection rate of PD‐L1 expression than tumor tissues (53.0% vs. 42.1%). No correlation was observed between them. Forty‐nine NSCLC patients received anti‐PD‐1/PD‐L1 immunotherapy (three with combined anti‐PD‐1/PD‐L1 and cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4), two with four cycles of combined immune checkpoint inhibitors [ICIs] plus chemotherapy and ICI monotherapy for maintenance). Patients with PD‐L1 expression on tissue or CTCs had a median progression‐free survival (mPFS) of 5.6 months (n = 36, 95% confidence interval [CI] 3.6–7.5 months), significantly longer than those without PD‐L1 detection (n = 9, mPFS of 1.4 months, 95% CI 1.3–1.5 months, log‐rank p = 0.032). The multivariable Cox proportional‐hazard model suggested that the tissue or CTC PD‐L1 expression was associated with a lower risk of progression (hazard ratio 0.45, 95% CI 0.21–0.98, p = 0.043). Conclusions CTCs and tumor tissues reveal heterogeneous expression of PD‐L1 in NSCLC patients. Patients with baseline PD‐L1 expression on CTCs or tissue showed prolonged mPFS and may help to identify the subsets of patients who potentially benefit from immunotherapy.

Abstract Background Immune checkpoint inhibitors (ICIs) have become one important therapeutic strategy for advanced non‐small‐cell lung cancer (NSCLC). It remains imperative to identify reliable and convenient biomarkers to predict both the efficacy and toxicity of immunotherapy, and tumor‐associated autoantibodies (TAAbs) are recognized as one of the promising candidates for this. Patients and Methods This study enrolled 97 advanced NSCLC patients with ICI‐based immunotherapy treatment, who were divided into a training cohort (n = 48) and a validation cohort (n = 49), and measured for the serum level of 35 TAAbs. According to the statistical association between the serum positivity and clinical outcome of each TAAb in the training cohort, a TAAb panel was developed to predict the progression‐free survival (PFS), and further examined in the validation cohort and in different subgroups. Similarly, another TAAb panel was derived to predict the occurrence of immune‐related adverse events (irAEs). Results In the training cohort, a 7‐TAAb panel composed of p53, CAGE, MAGEA4, GAGE7, UTP14A, IMP2, and PSMC1 TAAbs was derived to predict PFS (median PFS [mPFS] 9.9 vs. 4.3 months, p = 0.043). The statistical association between the panel positivity and longer PFS was confirmed in the validation cohort (mPFS 11.1 vs. 4.8 months, p = 0.015) and in different subgroups of patients. Moreover, another 4‐TAAb panel of BRCA2, MAGEA4, ZNF768, and PARP TAAbs was developed to predict the occurrence of irAEs, showing higher risk in panel‐positive patients (71.43% vs. 28.91%, p = 0.0046). Conclusions Collectively, our study developed and validated two TAAb panels as valuable prognostic biomarkers for immunotherapy.

Abstract Background Group A streptococcus is human-restricted gram-positive pathogen, responsible for various clinical presentations from mild epidermis infections to life threatened invasive diseases. Under COVID-19 pandemic,. the characteristics of the epidemic strains of GAS could be different. Purpose To investigate epidemiological and molecular features of isolates from GAS infections among children in Beijing, China between January 2020 and December 2021. Antimicrobial susceptibility profiling was performed based on Cinical Laboratory Sandards Institute. Distribution of macrolide-resistance genes, emm types, and superantigens was examined by polymerase chain reaction. Results 114 GAS isolates were collected which were frequent resistance against erythromycin (94.74%), followed by clindamycin (92.98%), tetracycline (87.72%). Emm12 (46.49%), emm1 (25.44%) were dominant emm types. Distribution of ermB, ermA, and mefA gene was 93.85%, 2.63%, and 14.04%, respectively. Frequent superantigenes identified were smeZ (97.39%), speG (95.65%), and speC (92.17%). Emm1 strains possessed smeZ, ssa, and speC, while emm12 possessed smeZ, ssa, speG, and speC. Erythromycin resistance was predominantly mediated by ermB. Scarlet fever strains harbored smeZ (98.81%), speC (94.05%). Impetigo strains harbored smeZ (88.98%), ssa (88.89%), and speC (88.89%). Psoriasis strains harbored smeZ (100%). Conclusions Under COVID-19 pandemic, our collections of GAS infection cutaneous diseases decreased dramatically. Epidemiological analysis of GAS infections among children during COVID-19 pandemic was not significantly different from our previous study. There was a correlation among emm, superantigen gene and disease manifestations. Long-term surveillance and investigation of emm types and superantigens of GAS prevalence are imperative.

Abstract Epithelial–mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a hallmark of the pathogenesis of proliferative vitreoretinopathy (PVR) that can lead to severe vision loss. Nevertheless, the precise regulatory mechanisms underlying the pathogenesis of PVR remain largely unknown. Here, we show that the expression of death-associated protein-like 1 (DAPL1) is downregulated in PVR membranes and that DAPL1 deficiency promotes EMT in RPE cells in mice. In fact, adeno-associated virus (AAV)-mediated DAPL1 overexpression in RPE cells of Dapl1-deficient mice inhibited EMT in physiological and retinal-detachment states. In a rabbit model of PVR, ARPE-19 cells overexpressing DAPL1 showed reduced ability to induce experimental PVR, and AAV-mediated DAPL1 delivery attenuated the severity of experimental PVR. Furthermore, a mechanistic study revealed that DAPL1 promotes P21 phosphorylation and its stabilization partially through NFκB (RelA) in RPE cells, whereas the knockdown of P21 led to neutralizing effects on DAPL1-dependent EMT inhibition and enhanced the severity of experimental PVR. These results suggest that DAPL1 acts as a novel suppressor of RPE-EMT and has an important role in antagonizing the pathogenesis of experimental PVR. Hence, this finding has implications for understanding the mechanism of and potential therapeutic applications for PVR.

Micro-light-emitting diodes (micro-LEDs) with high modulation rates and low power consumption could attract growing attention as visible light communication (VLC) technology advances. The designed and fabricated semi-polar micro-LEDs have achieved high bandwidth at low current injection due to the reduced quantum-confined Stark effect (QCSE), which was significantly greater than that of typical c-plane at the same current injection. Semi-polar green micro-LEDs got a −3 dB bandwidth that surpasses 500 MHz and 1 GHz at low current densities of 43.8 A/cm2 and 120.6 A/cm2, while blue micro-LEDs exceed 500 MHz at low current densities of 76.6 A/cm2, respectively. Additionally, the free space VLC system has shown semi-polar blue and green micro-LED transmission data rates of 3.495 Gbps (433 A/cm2) and 3.483 Gbps (402 A/cm2) respectively. Semi-polar micro-LEDs, which can achieve low power consumption and high bandwidth, are anticipated to play a significant role in the development of energy-efficient VLC in the future.

Objective: To explore the characteristics findings of early COVID-19 on chest thin-slice non-enhanced CT. Materials and methods: From November to December 2022, data from 153 patients with COVID-19 with positive chest CT findings confirmed by the Department of Infectious Diseases of our hospital were collected. All patients had relatively complete clinical data and underwent chest CT 1-14 days after the onset. The patients were divided into two groups according to their age (≤60 years old and >60 years old) and the time interval between the onset and CT examination (≤7 days old and >7 days old), and the differences in CT features between the two groups were compared. Result: Among 153 patients with COVID-19, the lung (100%), blood vessels (93.5%), airways (73.4%), and pleura (70.1%) were involved. The comparison between the age groups showed statistically significant differences in the number, location, size, volume, and band shadow of the lesions. There were statistically significant differences in the shape, density, organization, fibrosis, and pleural involvement of the lesions between the patients in the time interval between the onset and CT examination. Conclusion: Chest thin-slice CT can clarify the location and scope of early COVID-19. Some characteristics findings can help for accurate diagnosis and differentiation, such as the diversity of morphology, intrapleural and perivascular distribution, interstitial lesions with alveoli as a unit, early mixed ground-glass shadow often accompanied by obvious organization and fibrosis, localized thickening of the pleura, and few pleural effusions.

Background Besides the traditional roles of HBA1 and HBB, recent findings suggest that hemoglobin genes may have roles in other contexts.Objective In the present study, we aim to investigate a possible tumor-suppressor role of HBA1 and HBB in acute myeloid leukemia.Methods Quantitative real-time PCR (RT-qPCR) was performed to detect the expression levels of HBA1 and HBB in acute myeloid leukemia patients and AML cell lines. The transfected cells were analyzed for Cell Counting Kit-8 (CCK-8), apoptosis, and cell cycle assay.Results HBA1 and HBB genes were significantly decreased in acute myeloid leukemia patients and AML cell lines. Furthermore, in vitro approaches showed that overexpression of HBA1 and HBB inhibited proliferation, induced cell apoptosis, and blocked cell cycle process at the G2/M phase in K562 cells.Conclusion Our data indicated that HBA1 and HBB genes may be potential tumor-suppressor genes in acute myeloid leukemia.

Purpose: With the goal of increasing the translational efficiency of bone tissue engineering for practical clinical applications, biomimetic composite scaffolds combined with autologous endogenous growth factors for repairing bone defects have become a current research hotspot. In this study, we prepared a silk fibroin/chitosan/nanohydroxyapatite (SF/CS/nHA) composite biomimetic scaffold and then combined it with autologous concentrated growth factor (CGF) to explore the effect of this combination on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the efficiency of repairing critical radial defects. Methods: Three kinds of SF/CS/nHA composite biomimetic scaffolds with mass fractions of 3%, 4%, and 5% were prepared by vacuum freeze-drying and chemical cross-linking methods, and the characteristics of the scaffolds were evaluated. In vitro, BMSCs were seeded on SF/CS/nHA scaffolds, and then CGF was added. The morphology and proliferation of BMSCs were evaluated by live-dead staining, phalloidin staining, and CCK-8 assays. ALP staining, alizarin red staining, cellular immunofluorescence, RT–PCR, and Western blotting were used to detect the osteogenic differentiation of BMSCs. In vivo, a rabbit radius critical bone defect model was constructed, and the SF/CS/nHA-BMSC scaffold cell complex combined with CGF was implanted. The effect on bone defect repair was evaluated by 3D CT scanning, HE staining, Masson staining, and immunohistochemistry. Results: The characteristics of 4% SF/CS/nHA were the most suitable for repairing bone defects. In vitro, the SF/CS/nHA combined CGF group showed better adhesion, cell morphology, proliferation, and osteogenic differentiation of BMSCs than the other groups (P

Soil salinization is an environmental problem globally. Bermudagrass (Cynodon dactylon) has long been used for soil restoration in saline-alkali land. Urbanization and the compound planting pattern combining trees, bushes, and grasses induced shading are becoming one of the most significant environmental constraints on the management of bermudagrass, which directly affects photosynthetic characteristics. Salinity and shade have become the most important environmental constraints on lawn development and implementation. Previous studies have shown that the plant physiological response under combined stress was different from that under single stress. The purpose of this research was to investigate the effects of salinity stress, shade stress, and the combined stress on bermudagrass. Shade nets were used to simulate shade stress to 85% shade. The NaCl concentration gradient for salinity stress was 1.0% for 7 days, 1.5% for 7 days, and 2.0% for 13 days, respectively. The combined stress combines the two approaches mentioned previously. The results showed that the salinity stress significantly inhibited the plant height, leaf relative water content, chlorophyll content, the chlorophyll a fluorescence induction (OJIP) curve and other photosynthetic parameters of bermudagrass while increasing electrolyte leakage when compared with control. Shade stress significantly enhanced the plant height, chlorophyll content, electrolyte leakage, the OJIP curve, and other photosynthetic parameters. Under the combined stress, the plant height and relative water content did not change significantly, but the photosynthetic parameters such as chlorophyll content and the OJIP curve increased. Furthermore, under the combined stress, the photosynthesis-related genes were regulated. Salinity stress inhibited the photosynthetic ability of bermudagrass more than shade stress, while the combined stress exhibited a considerably better photosynthetic ability. These findings provide information for the usage of bermudagrass in salinized shade conditions.

The Moloney sarcoma oncogene (MOS) encodes a protein serine/threonine kinase and MOS is expressed at high levels in oocytes undergoing meiotic maturation. The MOS/MAPK pathway is normally required for the maintenance of microtubules and chromatin in a metaphasic state during the meiotic divisions. To determine the pathogenic genes in a female infertile patient due to large polar body oocytes, whole-exome sequencing was performed on the patient and available family members. We identified a novel homozygous missense mutation c.591T > G in MOS. Bioinformatics analysis showed that the mutation is harmful. These findings suggest that MOS mutation results in oocytes with a large polar body and poor embryonic development in patients. The MOS variant may regulate oocyte asymmetric division by MAPK/WAVE2/Arp2/3/actin signaling pathway. This will help to understand the comprehensive role of MOS in early human reproductive process and provide genetic markers for future genetic counseling for more individualized treatments.

Alopecia areata (AA) is a type of dermatological disease characterized by rapid and non-scarring hair loss of the scalp or body skin that may be related to genetic, immunological and physiological factors. It is now believed that AA is associated with oxidative stress, autoimmune disease, neuropsychological factors, pathogens, immune checkpoint inhibitors and microecological imbalance under the premise of host genetic susceptibility. In recent years, studies have revealed the significant role of the gut microbiome or metabolome in many aspects of human health. Diverse studies have revealed that the gut microbiome and metabolome have an important influence on skin conditions. This review highlights the relationship between AA and the gut microbiome or metabolome to provide novel directions for the prevention, clinical diagnosis and treatment of AA.

BackgroundThe epidemic of HIV infection among men who have sex with men (MSM) is a major public health concern in some parts of China, but data on trends in HIV incidence are limited. This study aimed to examine the trends in HIV incidence and factors associated with recent HIV infection among MSM in Jiangsu province, China, based on the limiting-antigen avidity enzyme immunoassay (LAg-Avidity-EIA) method.MethodsSix consecutive surveys were implemented among MSM throughout Jiangsu province from 2016 to 2021. Participants were recruited in three ways. Socio-demographic and behavioral information were collected through face-to-face interviews. Venous blood samples were taken to test for HIV and syphilis. HIV incidence was estimated using the LAg-Avidity-EIA method. Chi-square trend tests were used to observe trends over the years. Multivariate regression analyses were used to identify factors associated with recent HIV infection.ResultsA total of 15,401 participants were enrolled in the study. The prevalence of HIV infection ranged from 8.0 to 9.8%, with no consistent rise or fall over the years (P = 0.189). HIV incidence ranged from 5.0 to 9.0%, and no uptrend or downtrend was shown (P = 0.418). MSM who lived locally for more than 2 years (aOR = 1.366, P = 0.019), had a lack of comprehensive HIV knowledge (aOR = 1.643, P = 0.031), had engaged in unprotected anal intercourse (UAI) in the past 6 months (aOR = 7.373, P < 0.001), had been tested for HIV within 12 months (aOR = 1.292, P = 0.035), and tested positive for syphilis (aOR = 2.840, P < 0.001) were likely to be recently infected with HIV.ConclusionsHIV incidence among MSM has remained at a high level in Jiangsu province. In China, health education, condom use, and HIV/syphilis testing should continue to be top priorities for HIV prevention among MSM to reduce HIV transmission.

Oxidative stress induced by reactive oxygen species (ROS) is promising treatment approach for pancreatic ductal adenocarcinoma (PDAC), which is typically insensitive to conventional chemotherapy. In this study, BxPC-3 pancreatic cancer cell membrane-coated upconversion nanoparticles/ZnxMn1-xS core-shell nanoparticles (abbreviated as BUC@ZMS) were developed for tumor-targeted cancer therapy via synergistically oxidative stress and overcoming glutathione (GSH) overexpression. Using a combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT), the BUC@ZMS core-shell nanoparticles were able to elicit the death of pancreatic cancer cells through the high production of ROS. Additionally, the BUC@ZMS core-shell nanoparticles could deplete intracellular GSH and increase the sensitivity of tumor cells to oxidative stress. The in vivo results indicated that BUC@ZMS nanoparticles can accumulate specifically in tumor locations and suppress PDAC without generating obvious toxicity. Thus, it was determined that the as-prepared core-shell nanoparticles would be a viable treatment option for solid malignancies.

Abstract Aconitum carmichaelii (Fuzi) is a traditional Chinese medicine that has been widely used in the clinic to save the dying life for over several thousand years. However, the medicinal components of Fuzi in treating vascular senescence (VS) and its potential mechanism remain unclear. In this study, a network pharmacology method was used to explore the possible components and further validated by experiments to get a candidate compound, deoxyandrographolide (DA). DA restrains aging biomarkers, such as p16, p21, γH2A.X, and p53 in vitro and in vivo blood co‐culture studies. Histone deacetylase 1 (HDAC1), mouse double minute2 (MDM2), cyclin‐dependent kinase 4, and mechanistic target of rapamycin kinase (mTOR) are predicted to be the possible targets of DA based on virtual screening. Subsequent bio‐layer interferometry results indicated that DA showed good affinity capability with HDAC1. DA enhances the protein expression of HDAC1 in the angiotensin II‐induced senescence process by inhibiting its ubiquitination degradation. Loss of HDAC1 by CRISPR/Cas9 leads to the disappearance of DA's anti‐aging property. The enhancement of HDAC1 represses H3K4me3 (a biomarker of chromosomal activity) and improves chromosome stability. RNA sequencing results also confirmed our hypothesis. Our evidence illuminated that DA may achieve as a novel compound in the treatment of VS by improving chromosome stability.

RNA N6-melthyladenosine (m6A) can play an important role in regulation of various biological processes. Chicken ovary development is closely related to egg laying performance, which is a process primarily controlled by complex gene regulations. In this study, transcriptome-wide m6A methylation of the Wuhua yellow-feathered chicken ovaries before and after sexual maturation was profiled to identify the potential molecular mechanisms underlying chicken ovary development. The results indicated that m6A levels of mRNAs were altered dramatically during sexual maturity. A total of 1,476 differential m6A peaks were found between these two stages with 662 significantly upregulated methylation peaks and 814 downregulated methylation peaks after sexual maturation. A positive correlation was observed between the m6A peaks and gene expression levels, indicating that m6A may play an important role in regulation of chicken ovary development. Functional enrichment analysis indicated that apoptosis related pathways could be the key molecular regulatory pathway underlying the poor reproductive performance of Wuhua yellow-feathered chicken. Overall, the various pathways and corresponding candidate genes identified here could be useful to facilitate molecular design breeding for improving egg production performance in Chinese local chicken breed, and it might also contribute to the genetic resource protection of valuable avian species.

Leukemia stem cells (LSC) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSC of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in a H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSC, and that it promotes the initiation and maintenance of MLL-AF9-mediated AML. In addition, TWIST1 directly interacts and collaborates with HOXA9 in inducing AML in mice. Mechanistically, TWIST1 exerts its oncogenic function by activating the WNT5a/RAC1 axis. Collectively, our study uncovers a critical role of TWIST1 in LSC function and provides new mechanistic insights into the pathogenesis of MLL-AF9+ AML.

Saccharomycopsis fibuligera, which produces enzymes like amylase and protease as well as flavor substances like β-phenyl ethanol and phenyl acetate, plays a crucial role in traditional fermented foods. However, this strain still lacks a high-density fermentation culture, which has had an impact on the strain’s industrial application process. Therefore, this study investigated the optimization of medium ingredients and fermentation conditions for high-density fermentation of S. fibuligera Y1402 through single-factor design, Plackett–Burman design, steepest ascent test, and response surface analysis. The study found that glucose at 360.61 g/L, peptone at 50 g/L, yeast extract at 14.65 g/L, KH2PO4 at 5.49 g/L, MgSO4 at 0.40 g/L, and CuSO4 at 0.01 g/L were the best medium ingredients for S. fibuligera Y1402. Under these conditions, after three days of fermentation, the total colony count reached 1.79 × 108 CFU/mL. The optimal fermentation conditions were determined to be an initial pH of 6.0, an inoculum size of 1.10%, a liquid volume of 12.5 mL/250 mL, a rotation speed of 120 r/min, a fermentation temperature of 21 °C and a fermentation time of 53.50 h. When fermentation was conducted using the optimized medium and conditions, the total colony count achieved a remarkable value of 5.50 × 109 CFU/mL, exhibiting a substantial increase of nearly 31 times the original value in the optimal culture medium. This significant advancement offers valuable insights and a reference for the industrial-scale production of S. fibuligera.

Background: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. Methods: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. Results: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. Conclusions: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

3-Methylthio-1-propanol (3-Met) is an important flavor compound in various alcoholic beverages such as Baijiu and Huangjiu. To maintain the content of 3-Met in these alcoholic beverages, it is necessary to screen a micro-organism with high yield of 3-Met from the brewing environment. In this study, the ability of yeast strains from the Baijiu brewing to produce 3-Met was analyzed, aiming to obtain yeast with high-yield 3-Met, and its fermentation conditions were optimized. Firstly, 39 yeast strains were screened using 3-Met conversion medium. The results showed that the majority of the strains from Baijiu brewing sources could produce 3-Met, and nearly half of the strains produced more than 0.5 g/L of 3-Met. Among these, yeast F10404, Y03401, and Y8#01, produced more than 1.0 g/L of 3-Met, with yeast Y03401 producing the highest amount at 1.30 g/L. Through morphological observation, physiological and biochemical analysis, and molecular biological identification, it was confirmed that yeast Y03401 was a Saccharomyces cerevisiae. Subsequently, the optimal fermentation conditions for 3-Met production by this yeast were obtained through single-factor designs, Plackett–Burman test, steepest ascent path design and response surface methodology. When the glucose concentration was 60 g/L, yeast extract concentration was 0.8 g/L, L-methionine concentration was 3.8 g/L, initial pH was 4, incubation time was 63 h, inoculum size was 1.6%, shaking speed was 150 rpm, loading volume was 50 mL/250 mL, and temperature was 26 °C, the content of 3-Met produced by S. cerevisiae Y03401 reached a high level of 3.66 g/L. It was also noteworthy that, in contrast to other study findings, this yeast was able to create substantial amounts of 3-Met even in the absence of L-methionine precursor. Based on the clear genome of S. cerevisiae and its characteristics in 3-Met production, S. cerevisiae Y03401 had broad prospects for application in alcoholic beverages such as Baijiu.

The differences in chemical components, nutritional value, volatile organic compounds, antioxidant activity and α-glucosidase inhibiting capacity in vitro in coconut waters with different maturities (8, 10, and 12 months after pollination and germination height below 10 cm were named CW-8, CW-10, CW-2, and MCW, respectively) from the tall coconut variety were compared and analyzed. Results showed that as the maturity increased, the ash and reducing sugar in coconut water gradually decreased, while the protein content and fatty acids continued to increase. Potassium, phosphorus, and sodium in four coconut waters showed a trend of first increasing and then decreasing, and CW-12 had the highest content of 2133.85 mg/kg, 239.74 mg/kg, and 310.75 mg/kg, respectively. The volatile organic compounds (VOCs) present in higher amounts are alcohols and esters in coconut waters, among which 2-methylbutyl acetate, ethyl acetate monomer, and 2-methyl-1-propanol dimer were the characteristic volatile substances that distinguish MCW from the other three coconut waters. MCW has the best DPPH-scavenging and ferrous-ion-chelating ability (87.39% and 7.65%), while CW-8 had the highest hydroxyl and ABTS radicals scavenging rate (97.31% and 83.48%) and α-glucosidase inhibitory rate (81.36%). These results can provide support for the differential and high-value utilization of coconut water with different maturities.

Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability. The plausible molecular mechanism for di-isatropolone C formation is proposed, in which complex dehydrogenative C-C bond coupling may have happened to connect the two isatropolone C monomers. Like isatropolone C, di-isatropolone C shows the biological activity of inducing autophagy in HepG2 cells.

MYB98 is master regulator of the molecular network involved in pollen tube attraction. Until recently, it was unclear how this gene exhibits exclusively synergid cell-specific expression in ovule. Our recent study has established that a 16-bp-long SaeM element is crucial for its synergid cell-specific expression in ovule, and an 84-bp-long fragment harboring SaeM is sufficient to drive the process. In this study, we have developed a workflow to predict functional roles of potential transcription factors (TFs) putatively binding to the promoter region, taking MYB98 promoter as a test subject. After sequential assessment of co-expression pattern, network analysis, and potential master regulator identification, we have proposed a multi-TF model for MYB98 regulation. Our study suggests that ANL2, GT-1, and their respective homologs could be direct regulators of MYB98 and indicates that TCP15, TCP16, FRS9, and HB34 are likely master regulators of the majority of the TFs involved in its regulation. Comprehensive studies in the future are expected to offer more insights into such propositions. Developed workflow can be used while designing similar regulome-related studies for any other species and genes.

Accurate wind power forecasting is crucial for the safe, stable, and economical operation of green power systems. Multi-step forecasting of wind power has received increasing attention in recent years. From the perspective of machine learning, multi-step prediction can be transformed into a multi-task learning problem, i.e., multiple single-step prediction tasks. From a data-driven perspective, it is often difficult to respect the differences and relationships among multi-source heterogeneous data that are typically used in multi-step forecasting research, e.g., wind power and numerical weather prediction (NWP) data. This work proposes a multi-modal multi-task transformer network (M2TNet) model that can achieve ultra-short-term wind power multi-step forecasting based on multi-source heterogeneous data. The M2TNet is a unified framework that integrates multiple feature extractors, including a Transformer, a feature fusion layer-based fully-connected network, and a prediction terminal layer. The developed model applies multi-modal and multi-task learning strategies to effectively fuse multi-modal information and enable knowledge sharing among multiple single-step prediction tasks. In addition, the Transformer’s computing efficiency and ability to mine complex dependent data is exploited for joint learning of multi-source heterogeneous data. Data, including NWP and wind power, from a wind farm in Northeast China were used to validate M2TNet. The correlations between the input variables were analyzed using maximal information coefficient method to control the scale of the model. For prediction accuracy, the experimental results showed that, compared with the existing model, M2TNet reduced the root mean square error by 0.19%, 0.99%, 1.05%, and 1.53% in 4-, 8-, 12-, and 16-step ahead predictions, respectively. Furthermore, for computational efficiency, the training time of the existing model at a wind farm is 1.66 times that of M2TNet. This confirmed that the M2TNet model performs better in terms of prediction accuracy and computational efficiency. Our work illustrates the potential of M2TNet for large-scale wind farm applications.

Abstract Motivation Studies have shown that classifying cancer subtypes can provide valuable information for a range of cancer research, from aetiology and tumour biology to prognosis and personalized treatment. Current methods usually adopt gene expression data to perform cancer subtype classification. However, cancer samples are scarce, and the high-dimensional features of their gene expression data are too sparse to allow most methods to achieve desirable classification results. Results In this paper, we propose a deep learning approach by combining a convolutional neural network (CNN) and bidirectional gated recurrent unit (BiGRU): our approach, DCGN, aims to achieve nonlinear dimensionality reduction and learn features to eliminate irrelevant factors in gene expression data. Specifically, DCGN first uses the synthetic minority oversampling technique algorithm to equalize data. The CNN can handle high-dimensional data without stress and extract important local features, and the BiGRU can analyse deep features and retain their important information; the DCGN captures key features by combining both neural networks to overcome the challenges of small sample sizes and sparse, high-dimensional features. In the experiments, we compared the DCGN to seven other cancer subtype classification methods using breast and bladder cancer gene expression datasets. The experimental results show that the DCGN performs better than the other seven methods and can provide more satisfactory classification results.

Abstract Epithelial-mesenchymal transition (EMT) inducing transcription factor TWIST1 plays a vital role in cancer metastasis. How the tumor-suppressive E3 ligase, speckle-type POZ protein (SPOP), regulates TWIST1 in breast cancer remains unknown. In this study, we report that SPOP physically interacts with, ubiquitinates, and destabilizes TWIST1. SPOP promotes K63-and K48-linked ubiquitination of TWIST1, predominantly at K73, thereby suppressing cancer cell migration and invasion. Silencing SPOP significantly enhances EMT, which accelerates breast cancer cell migration and invasiveness in vitro and lung metastasis in vivo. Clinically, SPOP is negatively correlated with the levels of TWIST1 in highly invasive breast carcinomas. Reduced SPOP expression, along with elevated TWIST1 levels, is associated with poor prognosis in advanced breast cancer patients, particularly those with metastatic triple-negative breast cancer (TNBC). Taken together, we have disclosed a new mechanism linking SPOP to TWIST1 degradation. Thus SPOP may serve as a prognostic marker and a potential therapeutic target for advanced TNBC patients.

Abstract The generation and manipulation of spin-polarized current are critical for spintronic devices. In this work, we propose a mechanism to generate and switch spin-polarized current by an electric field in multiferroic tunnel junctions (MFTJs), with symmetric interface terminations in an antiparallel magnetic state. In such devices, different spin tunneling barriers are realized by the magnetoelectric coupling effect, resulting in a spin-polarized current. By reversing the electric polarization of the ferroelectric layer, the spin polarization of current is efficiently switched for the exchange of spin tunneling barriers. By first-principles quantum transport calculations, we show that a highly spin-polarized current is obtained and manipulated by the electric field in hafnia-based MFTJs based on the proposed mechanism. We also demonstrate that four resistance states are realized in Co/HfO2/Co junctions with asymmetric interface terminations. This work provides a promising approach for realizing the electrical control of spin current for spintronic applications.

Laryngeal carcinoma (LC) is the second most common malignant tumor of the head and neck. Due to its insidious nature, most patients have developed to the middle and late stages by the time they are diagnosed, missing the best treatment period. Thus, early detection, diagnosis and treatment are crucial to improve the prognosis of LC and enhance the quality of life of patients. In this study, a surface-enhanced Raman (SERS) sensing platform was developed by combining the magnetic beads (MBs) enrichment strategy and the antibody-DNA-mediated catalytic hairpin self-assembly (CHA) signal amplification technology. 4-Mercaptobenzoic acid (4-MBA) and hairpin DNA 1 (hpDNA1) were modified onto the surface of gold nanobipyramids (GNBPs) as SERS nanotags. Hairpin DNA 2 (hpDNA2) modified MBs were used as capture nanoprobes. Under the action of CHA and magnet-induced MBs enrichment, GNBPs can be assembled on the surface of MBs, forming high-density “hot spots” for the SERS signal enhancement. The results showed that the SERS sensing platform has the advantages of high sensitivity, high specificity and high reproducibility, with the limit of detection (LOD) low to pg/mL level. The expression level of CYFRA21-1 in serum of LC patients and healthy controls was successfully detected by the SERS sensing platform. The accuracy of the SERS results was verified by enzyme linked immunosorbent assay (ELISA). Therefore, this SERS sensor can be used for the detection of CYFRA21-1 in serum, providing a simple and reliable new method for the early diagnosis of LC.

Abstract Introduction Medical management of disorders of consciousness (DoC) is a growing issue imposing a major burden on families and societies. Recovery rates vary widely among patients with DoC, and recovery predictions strongly influence decisions on medical care. However, the specific mechanisms underlying different etiologies, consciousness levels, and prognoses are still unclear. Methods We analyzed the comprehensive cerebrospinal fluid (CSF) metabolome through liquid chromatography‐mass spectrometry. Metabolomic analyses were used to identify the metabolic differences between patients with different etiologies, diagnoses, and prognoses. Results We found that the CSF levels of multiple acylcarnitines were lower in patients with traumatic DoC, suggesting mitochondrial function preservation in the CNS, which might contribute to the better consciousness outcomes of these patients. Metabolites related to glutamate and GABA metabolism were altered and showed a good ability to distinguish the patients in the minimally conscious state and the vegetative state. Moreover, we identified 8 phospholipids as potential biomarkers to predict the recovery of consciousness. Conclusions Our findings shed light on the differences in physiological activities underlying DoC with different etiologies and identified some potential biomarkers used for DoC diagnosis and prognosis.

IntroductionObsessive-compulsive symptoms is a common psychological phenomenon among early adulthood college students, which are closely related to their parents’ parenting styles. Theoretical and some empirical studies have suggested the mediating role of perfectionism in this process, but this has not been confirmed, and the binary perspective of positive-negative perfectionism has not been addressed in this issue.MethodsThis study aimed to investigate the mediating role of perfectionism in the relationship between parenting styles and obsessive-compulsive symptoms among college students. A total of 661 college students participated in this study.ResultsNegative perfectionism mediated the relationship between negative parenting style and obsessive-compulsive symptoms among college students. Negative parenting style predicted obsessive-compulsive symptoms through its positive predictive effect on negative perfectionism. However, the mediating effect of positive perfectionism was not significant in this process.DiscussionThis study provides further evidence of the mechanisms underlying the occurrence of obsessive-compulsive symptoms, and offers new ideas for interventions for OCD.

IntroductionClear cell renal cell carcinoma (ccRCC) is the most prevalent type of urological carcinoma. Although targeted therapy and immunotherapy are usually employed, they often result in primary and acquired resistance. There is currently a lack of dependable biomarkers that can accurately anticipate the prognosis of ccRCC. Recent research has indicated the critical role of neutrophil extracellular traps (NETs) in the development, metastasis, and immune evasion of cancer. The aim of this study was to explore the value of NETs in the development and prognosis of ccRCC.MethodsClinical features and genetic expression information of ccRCC patients were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. NETs-related gene set were obtained from previous studies. A NETs-related gene signature was constructed based on TCGA data and validated using ICGC and E-MTAB-1980 databases. Furthermore, the immune microenvironment and responsiveness to anticancer medications in ccRCC patients with varying levels of NETs risks were investigated.ResultsA total of 31 NET-related genes were differently expressed between normal kidney and ccRCC tissues. 17 out of 31 were significantly associated with overall survival. After LASSO Cox regression analysis, nine NETs-related genes were enrolled to construct the NETs prognosis signature, and all the ccRCC patients from TCGA were divided into low and high risk group. This signature demonstrated excellent performance in predicting the overall survival of TCGA patients as well as the validation ICGC and E-MTAB-1980 patients. Additionally, the NETs signature was significantly correlated with immune infiltration and drug sensitivity.ConclusionsThe NETs signature established by the current study has prognostic significance in ccRCC, and may serve as a useful biomarker for patient stratification and treatment decisions. Further validation and clinical studies are required to fully translate these findings into clinical practice.

Summary: Probiotics play essential roles in immune modulation. Combining probiotics with cancer vaccines potentially can achieve a synergistic effect. To maximize the efficacy of probiotics, proper probiotics formulation is necessary. Herein, Lactobacillus rhamnosus and Bifidobacterium longum are coated with lipid membrane to achieve the goal of losing less activity and bettering colonization in colon. In the subcutaneous transplanted colon cancer mouse model, probiotics formulation showed potent preventive and therapeutic efficacy, and the efficacy could be further improved by combining with cancer nanovaccines. Probiotics formulation can perform as immune adjuvants to enhance the innate immune response or as in-situ cancer vaccines. In the study of preventing chemical-induced orthotopic colon cancer model, probiotics formulation alone efficiently reduced tumor number in colon and the efficacy is improved by combining with cancer nanovaccines. All in all, the studies demonstrated that probiotics formulation can assist to maximize the efficacy of cancer nanovaccines.

The decreased antioxidant capacity in the retinal pigment epithelium (RPE) is the hallmark of retinal degenerative diseases including age-related macular degeneration (AMD). Nevertheless, the exact regulatory mechanisms underlying the pathogenesis of retinal degenerations remain largely unknown. Here we show in mice that deficiencies in Dapl1, a susceptibility gene for human AMD, impair the antioxidant capacity of the RPE and lead to age-related retinal degeneration in the 18-month-old mice homozygous for a partial deletion of Dapl1. Dapl1-deficiency is associated with a reduction of the RPE's antioxidant capacity, and experimental re-expression of Dapl1 reverses this reduction and protects the retina from oxidative damage. Mechanistically, DAPL1 directly binds the transcription factor E2F4 and inhibits the expression of MYC, leading to upregulation of the transcription factor MITF and its targets NRF2 and PGC1α, both of which regulate the RPE's antioxidant function. When MITF is experimentally overexpressed in the RPE of DAPL1 deficient mice, antioxidation is restored and retinas are protected from degeneration. These findings suggest that the DAPL1-MITF axis functions as a novel regulator of the antioxidant defense system of the RPE and may play a critical role in the pathogenesis of age-related retinal degenerative diseases.

Aims and backgroundHepatic hydrothorax, which presents as an unexplained pleural effusion, is one of the important complications in patients with end-stage cirrhosis. It has a significant correlation with prognosis and mortality. The aim of this clinical study was to detect the risk factors for hepatic hydrothorax in patients with cirrhosis and to better understand potentially life-threatening complications.MethodsRetrospectively, 978 cirrhotic patients who were hospitalized at the Shandong Public Health Clinical Center from 2013 to 2021 were involved in this study. They were divided into the observation group and the control group based on the presence of hepatic hydrothorax. The epidemiological, clinical, laboratory, and radiological characteristics of the patients were collected and analyzed. ROC curves were used to evaluate the forecasting ability of the candidate model. Furthermore, 487 cases in the experimental group were divided into left, right, and bilateral groups, and the data were analyzed.ResultsThe patients in the observation group had a higher proportion of upper gastrointestinal bleeding (UGIB), a history of spleen surgery, and a higher model for end-stage liver disease (MELD) scores compared with the control group. The width of the portal vein (PVW) (P = 0.022), prothrombin activity (PTA) (P = 0.012), D-dimer (P = 0.010), immunoglobulin G (IgG) (P = 0.007), high-density lipoprotein cholesterol (HDL) (P = 0.022), and the MELD score were significantly associated with the occurrence of the hepatic hydrothorax. The AUC of the candidate model was 0.805 (P < 0.001, 95% CI = 0.758–0.851). Portal vein thrombosis was more common in bilateral pleural effusion compared with the left and right sides (P = 0.018).ConclusionThe occurrence of hepatic hydrothorax has a close relationship with lower HDL, PTA, and higher PVW, D-dimer, IgG, and MELD scores. Portal vein thrombosis is more common in cirrhotic patients with bilateral pleural effusion compared to those with unilateral pleural effusion.

Because of its excellent stress resistance and forage quality, the forage bermudagrass hybrid population had attracted the attention of scientific researchers in recent years. Studying its diversity could promote the breeding of desirable varieties. The variability in agronomic traits including fresh weight, dry weight, ash content, crude protein content, crude fat, phosphorus content, and relative feed value for 56 bermudagrass was investigated using Wrangler as an experimental reference. Grey correlation analysis and cluster analysis were employed to screen bermudagrass with high yield and superior quality. WCF-34 had the highest 2-year fresh weight (109,773.3 kg/ha), WCF-37 had the highest 2-year dry weight (31,951.6 kg/ha), WCF-24 had the lowest Ash content (7.46%), WCF-26 had the highest crude protein content (16.27%), WCF-27 had the highest curde fat content (3.58%), WCF-13 had the highest P content (0.45%), and WCF-42 had the highest relative feed value (95.32). Combining the results of grey relational analysis and cluster analysis, WCF-42, WCF-34, WCF-38, WCF-37, and WCF-40 were selected as high-quality bermudagrass. Through comprehensive analysis of the agronomic characters of bermudagrass, five bermudagrass were selected, the outcomes of this study would provide a theoretical basis for the breeding and genetic enhancement of bermudagrass.

IntroductionIn the world, the incidence of breast cancer has surpassed that of lung cancer, and it has become the first malignant tumor among women. Triple-negative breast cancer (TNBC) shows an extremely heterogeneous malignancy toward high recurrence, metastasis, and mortality, but there is a lack of effective targeted therapy. It is urgent to develop novel molecular targets in the occurrence and therapeutics for TNBC, and novel therapeutic strategies to block the recurrence and metastasis of TNBC.MethodsIn this study, CTSL (cathepsin L) expression in tissues and adjacent tissues of TNBC patients was monitored by immunohistochemistry and western blots. The correlations between CTSL expressions and clinicopathological characteristics in the patient tissues for TNBC were analyzed. Cell proliferation, migration, and invasion assay were also performed when over-expressed or knocked-down CTSL.ResultsWe found that the level of CTSL in TNBC is significantly higher than that in the matched adjacent tissues, and associated with differentiated degree, TNM Stage, tumor size, and lymph node metastatic status in TNBC patients. The high level of CTSL was correlated with a short RFS (p

Introduction: The middle and lower reaches of the Yangtze River basin (hereafter MLYRB) are one of the most important wintering grounds for waterbirds along the East Asian-Australasian Flyway (EAAF). Climate change and human activities have greatly altered the habitats of waterbirds in this region.Methods: The potential distribution of suitable habitats for the Siberian crane (Grus leucogeranus) in the MLYRB was projected using Maximum Entropy Models (MaxEnt) and three Global Climate Models (GCMs). Additionally, estimations for temperature and precipitation before 2060 were made using CMIP6 multi-model and multi-scenario data.Results: 1) the MaxEnt model was highly applicable (AUC = 0.939) for analyzing the suitable habitat distribution and climatic suitability of Siberian cranes in the study area; 2) Precipitation of the driest quarter and altitude were the main factors affecting the potential suitable habitat distribution of Siberian cranes, accounting for 40% of the total contribution rate each; 3) The climatically suitable areas for the distribution of suitable habitats of Siberian cranes in the study area was mainly concentrated in parts of Poyang Lake, Dongting Lake, Taihu Lake, and the mainstream of the Yangtze River; 4) In the BCC-CSM2-MR, CanESM5, and CNRM-CM6-1 models, the suitable habitat area for Siberian cranes is expected to decrease under different SSP scenarios from 2021 to 2060 compared to 1970–2000.Discussion: The BCC-CSM2-MR model’s SSP2-4.5 scenario shows the most significant decline in the suitable habitat area for Siberian cranes, with a maximum decrease of approximately 35.7%, followed by a maximum decrease of about 26.2% and 16.4% under the CNRM-CM6-1 and CanESM5 models’ SSP2-4.5 scenario, respectively. In general, the suitable habitat areas for Siberian cranes are projected to decline, indicating the need for comprehensive evaluation and uncertainty research using more models.