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Study region: Xiangjiang basin, a humid subtropical inland region of central-south China. Study focus: Tropical Cyclones (TCs) usually cause extreme precipitation events (EPEs) and flooding in both coastal and inland areas, resulting in severe economic losses. However, TC impacts in inland regions were seldom investigated. This study provided a climatological view of TCs, TC-induced EPEs and flooding in the Xiangjiang basin over the past nearly 70 years, and examined their relationships with ENSO using data from 127 meteorological stations, 22 hydrological stations, and TC tracks. New hydrological insights for the region: Xiangjiang basin averaged five TC visits annually, primarily between July and September, when the majority of EPEs and flooding associated with TCs occurred. Despite the relatively low frequency (less than 30 %) of TC-induced EPEs and flooding compared to coastal regions, their magnitudes were comparable to or even exceeded those in coastal regions. These influences were modulated by ENSO. In neutral years, the frequency and magnitude of TC-induced EPEs were greatest due to higher TC track density and frequency. Also, TC tracks shifted westward, increasing the likelihood of extreme TC flooding in neutral years. The southeast of the basin faced the highest risk of TC-related disasters, especially in neutral years. This paper highlights the need to strengthen monitoring and prevention for TC-induced disasters in inland regions.

Abstract To investigate the unmet needs for rehabilitation services among middle-aged and older adults in Chengdu, Sichuan, China, and identify the associated factors. This cross-sectional study was conducted on middle-aged and older adults in Chengdu, Sichuan, China, between 2015 and 2016. The questionnaire included demographic data and questions about rehabilitation needs. Multivariable logistic regression analysis was used to identify the associated factors of unmet needs for rehabilitation services. Among 663 participants, 91.70% needed medical rehabilitation (608/663), 26.55% of who need auxiliary equipment (176/663), 77.07% of who need daily care and social participation (511/663), and 79.34% of who need recreational therapy activities (526/663), while

Abstract Background Amino acid property-aware phylogenetic analysis (APPA) refers to the phylogenetic analysis method based on amino acid property encoding, which is used for understanding and inferring evolutionary relationships between species from the molecular perspective. Fast Fourier transform (FFT) and Higuchi’s fractal dimension (HFD) have excellent performance in describing sequences’ structural and complexity information for APPA. However, with the exponential growth of protein sequence data, it is very important to develop a reliable APPA method for protein sequence analysis. Results Consequently, we propose a new method named FFP, it joints FFT and HFD. Firstly, FFP is used to encode protein sequences on the basis of the important physicochemical properties of amino acids, the dissociation constant, which determines acidity and basicity of protein molecules. Secondly, FFT and HFD are used to generate the feature vectors of encoded sequences, whereafter, the distance matrix is calculated from the cosine function, which describes the degree of similarity between species. The smaller the distance between them, the more similar they are. Finally, the phylogenetic tree is constructed. When FFP is tested for phylogenetic analysis on four groups of protein sequences, the results are obviously better than other comparisons, with the highest accuracy up to more than 97%. Conclusion FFP has higher accuracy in APPA and multi-sequence alignment. It also can measure the protein sequence similarity effectively. And it is hoped to play a role in APPA’s related research.

Aberrant alternative splicing is one of the important causes of cancer. Polypyrimidine tract binding protein 1 (PTBP1) has been found to be involved in splicing regulation in a variety of tumors. Here, we observed significant up-regulation of PTBP1 in primary hepatocellular carcinoma (HCC) tissues. High levels of PTBP1 expression were associated with poor prognosis and increased metastatic potential in HCC. In vitro studies demonstrated that elevated PTBP1 promoted both migration and invasion by HCC cells. In contrast, knockdown of PTBP1 significantly inhibited the migration and invasion of HCC cells in vitro. Further, up-regulation of PTBP1 markedly accumulated the expression of oncogenic isoform of NUMB, NUMB-PRRL. We observed two isoforms of NUMB, NUMB-PRRL and NUMB-PRRS exhibit opposite function in HCC cells, which partially explain PTBP1 plays the tumor promoting roles in a NUMB splicing-dependent manner. In summary, our study indicates that PTBP1 may serve as an oncogene in HCC patients by regulating the alternative splicing of NUMB exon 9 and could potentially serve as a prognostic indicator.

ObjectiveTo analyze the application effect of pelvic floor rehabilitation exercise in postoperative patients with cervical cancer and the factors influencing their self-efficacy.Methods120 postoperative patients with cervical cancer from January 2019 to January 2022 from the Department of Rehabilitation, Aeronautical Industry Flying Hospital, Bayi Orthopaedic Hospital and Southwest Medical University Affiliated Hospital of Traditional Chinese Medicine, and the Department of Obstetrics and Gynecology, Chengdu Seventh People’s Hospital, and the Department of Oncology, Sichuan Provincial People’s Hospital were selected for the study. They were divided into routine group (n=44, applied routine care) and exercise group (n=76, applied routine care + pelvic floor rehabilitation exercise) according to the different perioperative care programs. The perioperative indicators, bladder function recovery rate and urinary retention incidence, urodynamic indicators, and pelvic floor distress inventory-short form 20 (PFDI-20) scores were compared between the 2 groups. The general data, PFDI-20 scores and broome pelvic muscle self-efficacy scale (BPMSES) scores of patients in the exercise group were investigated and analyzed individually to investigate the factors influencing the self-efficacy of patients with pelvic floor rehabilitation exercise after cervical cancer surgery.ResultsThe time of first anal exhaust, urine tube retention and hospitalization after surgery were shorter in the exercise group than in the routine group (P0.05). At 3 months after surgery, the PFDI-20 scores were higher in both groups than before surgery, and the exercise group was lower than the routine group (P

In organisms, ribonucleic acid (RNA) plays an essential role. Its function is being discovered more and more. Due to the conserved nature of RNA sequences, its function mainly depends on the RNA secondary structure. The discovery of an approximate relationship between two RNA secondary structures helps to understand their functional relationship better. It is an important and urgent task to explore structural similarities from the graphical representation of RNA secondary structures. In this paper, a novel graphical analysis method based on the triple vector curve representation of RNA secondary structures is proposed. A combinational method involving a discrete wavelet transform (DWT) and fractal dimension with sliding window is introduced to analyze and compare the graphs derived from feature extraction; after that, the distance matrix is generated. Then, the distance matrix is analyzed by clustering and visualized as a clustering tree. RNA virus and noncoding RNA datasets are applied to perform experiments and analyze the clustering tree. The results show that the proposed method yields more accurate results in the comparison of RNA secondary structures.

The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.

Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1–Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop an RNA-binding protein (RBP)-based signature for risk stratification and guiding clinical therapy in gastric cancer.Methods: Based on survival-related RBPs, an RBP-based signature was established by LASSO regression analysis in TCGA dataset. Kaplan–Meier curves were drawn between high- and low-risk groups. The predictive efficacy of this signature was assessed via ROCs at 1-, 3-, and 5-year survival. Its generalizability was verified in an external dataset. Following adjustment with other clinicopathological characteristics, the independency of survival prediction was evaluated via multivariate Cox regression and subgroup analyses. GSEA was utilized in identifying activated pathways in two groups. Stromal score, immune score, tumor purity, and infiltration levels of 22 immune cells were determined in each sample via the ESTIMATE and CIBERSORT algorithms. The sensitivity to chemotherapy drugs was assessed through the GDSC database.Results: Data showed that patients with high risk exhibited unfavorable clinical outcomes than those with low risk. This signature possessed good performance in predicting 1-, 3-, and 5-year survival and can be independently predictive of patients' survival. Calcium, ECM receptor interaction, and focal adhesion were highly enriched in high-risk samples. High-risk samples presented increased stromal and immune scores and reduced tumor purity. Moreover, this signature presented close relationships with immune infiltrations. Low-risk specimens were more sensitive to sorafenib, gefitinib, vinorelbine, and gemcitabine than high-risk specimens.Conclusion: This RBP-based signature may be a promising tool for predicting clinical outcomes and guiding clinical therapy in gastric cancer.

In order to improve the performance of the traditional constant-width herringbone grooved journal bearing in a computed tomography tube under a high-temperature environment, the present study designed a convergent herringbone grooved journal bearing (HGJB) structure lubricated by liquid metal. The bearing oil film thickness and the Reynolds equation considering the influence of turbulence are established and solved by using the finite difference method in the oblique coordinate system. The performance of the two bearings was compared, and the static and dynamic performance change trends of the two bearing structures under different eccentricities were systematically studied. The results show that the convergent herringbone grooved journal bearings are superior to the constant-width herringbone grooved journal bearings in terms of bearing capacity and stiffness coefficient. At the same time, the influence of structural parameters, such as the number of grooves, helix angle, groove to ridge ratio, groove depth on the performance of the constant-width herringbone grooved journal bearings, and the convergent herringbone grooved journal bearings was studied. Finally, we conclude that the performance of the convergent herringbone grooved journal bearings is optimal when the number of grooves is 15–20, the helix angle is 30°–45°, the ratio of the groove to ridge is 1, and the groove depth is 0.02 mm –0.024 mm. This research has provided the thinking and reference basis for the design of liquid metal bearings for high-performance CT equipment.

Aiming at the problem that the current coefficient of restitution model cannot effectively predict energy dissipation in the multi-body system collision process, a coefficient of restitution model considering the yield strength is proposed in this article. As an important parameter for energy loss and material deformation prediction during collision, the coefficient of restitution has an important influence on the accurate calculation of contact force. The current main coefficient of restitution models are compared and analyzed in this article. In view of the large difference between the results obtained by different models on the same parameter, through the use of ANSYS/LS–DYNA for dynamic simulation, the influence of different yield strengths on the coefficient of restitution is studied. Then, the article establishes a new coefficient of restitution model considering the yield strength combined with the J–G model, and verifies the effectiveness of the model in the article using experimental results. At the same time, the article compares the new coefficient of restitution model with the constant coefficient of restitution model, and further studies the effect of the coefficient of restitution on the dynamic results.

Pseudomonas aeruginosa (P. aeruginosa) is a major opportunistic human pathogen, causing serious nosocomial infections among immunocompromised patients by multi-determinant virulence and high antibiotic resistance. The CzcR-CzcS signal transduction system in P. aeruginosa is primarily involved in metal detoxification and antibiotic resistance through co-regulating cross-resistance between Zn(II) and carbapenem antibiotics. Although the intracellular regulatory pathway is well-established, the mechanism by which extracellular sensor domain of histidine kinase (HK) CzcS responds to Zn(II) stimulus to trigger downstream signal transduction remains unclear. Here we determined the crystal structure of the CzcS sensor domain (CzcS SD) in complex with Zn(II) at 1.7 Å resolution. This is the first three-dimensional structural view of Zn(II)-sensor domain of the two-component system (TCS). The CzcS SD is of α/β-fold in nature, and it senses the Zn(II) stimulus at micromole level in a tetrahedral geometry through its symmetry-related residues (His55 and Asp60) on the dimer interface. Though the CzcS SD resembles the PhoQ-DcuS-CitA (PDC) superfamily member, it interacts with the effector in a novel domain with the N-terminal α-helices rather than the conserved β-sheets pocket. The dimerization of the N-terminal H1 and H1' α-helices is of primary importance for the activity of HK CzcS. This study provides preliminary insight into the molecular mechanism of Zn(II) sensing and signaling transduction by the HK CzcS, which will be beneficial to understand how the pathogen P. aeruginosa resists to high levels of heavy metals and antimicrobial agents.

Despite its side-effects, docetaxel (DTX) remains a first-line treatment against castration resistant prostate cancer (CRPC). Therefore, strategies to increase its anti-tumor efficacy and decrease its side effects are critically needed. Targeting of the constitutive endoplasmic reticulum (ER) stress in cancer cells is being investigated as a chemosensitization approach. We hypothesized that the simultaneous induction of ER-stress and suppression of PI3K/AKT survival pathway will be a more effective approach. In a CRPC cell line, C4-2B, we observed significant (p

Castration-resistant progression of prostate cancer after androgen deprivation therapies remains the most critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor (AR) activity is an established driver of castration-resistant progression, and upregulation of the full-length AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been implicated to contribute to the resurgent AR activity. We reported previously that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of both AR-FL and AR-Vs. In the present study, we further showed that the effect of PPD on AR expression and target genes was independent of androgen. PPD treatment resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft tumors with endogenous expression of AR-FL and AR-Vs. This was accompanied by a decline in serum prostate-specific antigen levels as well as a decrease in AR levels and mitoses in the tumors. Notably, the 22Rv1 xenograft tumors were resistant to growth inhibition by the next-generation anti-androgen enzalutamide. The present study represents the first to show the preclinical efficacy of PPD in inhibiting castration-resistant progression and growth of prostate cancer. The findings provide a rationale for further developing PPD or its analogues for prostate cancer therapy.