Essential role of N-terminal SAM regions in STIM1 multimerization and function.

The single-pass transmembrane protein Stromal Interaction Molecule 1 (STIM1), located in the endoplasmic reticulum (ER) membrane, possesses two main functions: It senses the ER-Ca2+ concentration and directly binds to the store-operated Ca2+ channel Orai1 for its activation when Ca2+ recedes. At high resting ER-Ca2+ concentration, the ER-luminal STIM1 domain is kept monomeric but undergoes di/multimerization once stores are depleted. Luminal STIM1 multimerization is essential to unleash the STIM C-terminal binding site for Orai1 channels. However, structural basis of the luminal association sites has so far been elusive. Here, we employed molecular dynamics (MD) simulations and identified two essential di/multimerization segments, the α7 and the adjacent region near the α9-helix in the sterile alpha motif (SAM) domain. Based on MD results, we targeted the two STIM1 SAM domains by engineering point mutations. These mutations interfered with higher-order multimerization of ER-luminal fragments in biochemical assays and puncta formation in live-cell experiments upon Ca2+ store depletion. The STIM1 multimerization impeded mutants significantly reduced Ca2+ entry via Orai1, decreasing the Ca2+ oscillation frequency as well as store-operated Ca2+ entry. Combination of the ER-luminal STIM1 multimerization mutations with gain of function mutations and coexpression of Orai1 partially ameliorated functional defects. Our data point to a hydrophobicity-driven binding within the ER-luminal STIM1 multimer that needs to switch between resting monomeric and activated multimeric state. Altogether, these data reveal that interactions between SAM domains of STIM1 monomers are critical for multimerization and activation of the protein.

Electroacupuncture stimulation modulates functional brain connectivity in the treatment of pediatric cerebral palsy: a case report.

Background: Pediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified. Methods: We present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison. Results: After a 12-month follow-up, notable advancements were observed in the patient's language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors. Conclusion: This is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP.

Anti-UV Microgel Based on Interfacial Polymerization to Decrease Skin Irritation of High Permeability UV Absorber Ethylhexyl Methoxycinnamate.

Ethylhexyl methoxycinnamate (EHMC) is frequently employed as a photoprotective agent in sunscreen formulations. EHMC has been found to potentially contribute to health complications as a result of its propensity to produce irritation and permeate the skin. A microgel carrier, consisting of poly(ethylene glycol dimethacrylate) (pEDGMA), was synthesized using interfacial polymerization with the aim of reducing the irritation and penetration of EHMC. The thermogravimetric analysis (TGA) indicated that the EHMC content accounted for 75.72% of the total composition. Additionally, the scanning electron microscopy (SEM) images depicted the microgel as exhibiting a spherical morphology. In this study, the loading of EHMC was demonstrated through FTIR and contact angle tests. The UV resistance, penetration, and skin irritation of the EHMC-pEDGMA microgel were additionally assessed. The investigation revealed that the novel sunscreen compound, characterized by limited dermal absorption, had no irritant effects and offered sufficient protection against ultraviolet radiation.

Integration of machine learning for developing a prognostic signature related to programmed cell death in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction. METHOD: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models. RESULT: Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis. CONCLUSION: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC.

[Exposure characteristics and health risk assessment of 97 typical chemical pollutants in human serum].

Rapid industrial and agricultural developments in China have led to the wide use and discharge of chemical products and pesticides, resulting in extensive residues in environmental media. These residues can enter the human body through various pathways, leading to high exposure risks and health hazards. Because the human body is exposed to a variety of chemical pollutants, accurately quantifying the exposure levels of these pollutants in the human body and evaluating their health risks are of great importance. In this study, the serum concentrations of 97 typical chemical pollutants of 60 adults in central China were simultaneously determined using solid-phase extraction coupled with gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS). In this method, 200 µL of a serum sample was mixed with 10 µL of an isotope-labeled internal standard solution. The sample was vortexed and refrigerated overnight at 4 ℃. Each sample was then deproteinized by the addition of 200 µL of 15% formic acid aqueous solution and vortexed. The serum sample was loaded into a preconditioned Oasis® PRiME HLB SPE cartridge and rinsed with 3 mL of methanol-water (6∶1, v/v). The SPE cartridge was subsequently vacuumed. The analytes were eluted with 3 mL of dichloromethane followed by 3 mL of n-hexane. The eluent was concentrated to near dryness under a gentle nitrogen stream and reconstituted with 100 µL of acetone. The samples were determined by GC-MS/MS and separated on a DB-5MS capillary column (30 m×0.25 mm×0.25 µm) with temperature programming. The column temperature was maintained at 70 ℃ for 2 min, increased at a rate of 25 ℃/min to 150 ℃, increased at a rate of 3 ℃/min to 200 ℃, and then held for 2 min. Finally, the column temperature was increased at a rate of 8 ℃/min to 300 ℃ and maintained at this temperature for 8 min. The samples were detected in multiple-reaction monitoring (MRM) mode and quantitatively analyzed using the internal standard method. Multiple linear regression models were used to analyze the effects of demographic characteristics, lifestyle habits, and diet on the concentrations of the chemical pollutants in the serum samples, and known biomonitoring equivalents (BEs) and human biomonitoring (HBM) values were combined to compute hazard quotients (HQs) and hazard indices (HIs) and evaluate the health risks of single and cumulative exposures to the chemical pollutants. The results showed that the main pollutants detected in human serum were organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The detection rates of eight pollutants, including hexachlorobenzene (HCB) (100%), pentachlorophenol (PCP) (100%), p,p'-dichlorodiphenylene (p,p'-DDE) (100%), PCB-138 (100%), PCB-153 (98.3%), ß-hexachlorocyclohexane (ß-HCH) (91.7%), fluorene (Flu) (85.0%), and anthracene (Ant) (75.0%), were greater than 70%. The serum levels of ß-HCH were higher in females than in males, and age was positively correlated with exposure to p,p'-DDE, PCB-138, PCB-153, and ß-HCH. Increased exposure levels to p,p'-DDE and ß-HCH may be associated with a high frequency of meat intake, whereas increased exposure level to PCP may be associated with a high frequency of vegetable intake. The serum HQ of PCP was greater than 1 in 6.7% of the samples, and no risk was observed for HCB and p,p'-DDE exposure in the study population. Approximately 28.3% of the study subjects had HI values greater than 1. Overall, the general adult population in this region is widely exposed to a wide range of chemical pollutants, and gender, age, and diet are likely to be the main factors influencing the concentration of chemical pollutants. The health risk of single and compound exposures to chemical pollutants should not be ignored.

Effects of Plant Regulators on the Seed Germination and Antioxidant Enzyme Activity of Cotton under Compound Salt Stress.

Salinity stress significantly hampers cotton seed germination and seedling growth. Employing plant growth regulators stands out as an effective strategy to mitigate salt stress. In this study, we assessed the impact of varying concentrations of natural composite salt conditions (0%, 0.6%, and 1.2%) on cotton seed germination, seedling growth, and physiology. Additionally, we explored the effects of compound sodium nitrophenolate (CSN: 2 mg·L-1 and 10 mg·L-1), 24-epibrassinolide (EBR: 0.02 mg·L-1 and 0.1 mg·L-1), and gibberellic acid (GA: 60 mg·L-1 and 300 mg·L-1), against a control (CK: distilled water) group. The results indicate that with an increase in the composite salt concentration, the germination potential (GP) and germination rate (GR) of cotton seeds gradually decrease. Simultaneously, the fresh weight and root vitality of seedlings also correspondingly decrease, while the degree of membrane lipid peroxidation increases. Under high-salt (1.2%) conditions, soaking treatments with CSN and EBR significantly enhance both GP (45-59% and 55-64%) and GR (30-33% and 39-36%) compared to the CK. However, the GA treatment does not increase the GP and GR of cotton. Moreover, under high-salt (1.2%) conditions, CSN and EBR treatments result in the increased activities of superoxide dismutase (56-66% and 71-80%), peroxidase (20-24% and 37-51%), and catalase (26-32% and 35-46%). Consequently, cotton exhibits a relatively good tolerance to natural composite salts. Soaking treatments with CSN and EBR effectively improve cotton germination by enhancing antioxidant enzyme activities, thereby strengthening cotton's tolerance to salt stress. These findings offer new insights for enhancing the salt tolerance of cotton.

Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.

Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity. We report herein a nanocapsule enzyme therapeutic based on lactate oxidase, which reduces lactate concentrations and releases immunostimulatory hydrogen peroxide, averting tumor immunosuppression and improving the efficacy of immune checkpoint blockade treatment. As demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer, this enzyme therapeutic affords an effective tool toward more effective cancer immunotherapy.

Value of serum free prostate-specific antigen density in the diagnosis of prostate cancer.

PURPOSE: To investigate the value of serum free prostate-specific antigen density (fPSAD) in the diagnosis of prostate cancer (PCa). METHODS: The data of 558 patients who underwent transrectal ultrasound-guided prostate biopsy were retrospectively analyzed. According to the pathological results, the patients were divided into a PCa group and a benign prostatic hyperplasia (BPH) group. Receiver operating characteristic curves were plotted, based on which the sensitivity, specificity, Youden index, concordance, and kappa values of free prostate-specific antigen (fPSA), the free-to-total f/tPSA, prostate-specific antigen density (PSAD), the free-to-total (f/t)/PSAD ratio, and fPSAD were compared. The patients were divided into three groups by PSA levels (PSA < 4 ng/mL, PSA = 4-10 ng/mL, and PSA > 10 ng/mL), into three groups by age (age < 60 year, age = 60-80y, and age > 80 years), and into two groups by prostate volume (PV) (PV ≤ 80 mL and PV > 80 mL) to compare the sensitivity, specificity, and concordance of indicators. RESULTS: tPSA, PSAD, (f/t)/PSAD, and fPSAD had high accuracy in predicting PCa with AUC values of 0.820, 0.900, 0.846, and 0.867. fPSAD showed lower diagnostic sensitivity but significantly higher specificity and concordance for PCa than tPSA, f/tPSA, (f/t)/PSAD, or PSAD. Thus, fPSAD had the highest accuracy in the diagnosis of PCa. In the groups with different PSA, age, and PV stratification, the concordance of fPSAD was significantly higher (88.61%, 90.74%, and 90.38%) than that of other indicators. CONCLUSION: With the optimal cutoff value of 0.062, fPSAD has a higher diagnostic value for PCa than tPSA, f/tPSA, (f/t)/PSAD, and PSAD, and can well predict the risk of PCa, significantly improve the clinical diagnostic rate of PCa, and reduce unnecessary biopsy.

Topological spatial differentiation via complex amplitude filtering in Fourier space.

Various approaches to implementing optical analog differentiation have been studied extensively and applied in edge-based image processing. Here, we report a topological optical differentiation scheme based on complex amplitude filtering, i.e., amplitude and spiral phase modulation in Fourier space. The isotropic and anisotropic multiple-order differentiation operations are demonstrated both theoretically and experimentally. Meanwhile, we also achieve multiline edge detection corresponding to the differential order for the amplitude and phase objects. This proof-of-principle work could open up new avenues for engineering a nanophotonic differentiator and realizing a more compact image-processing system.

Construction and validation of a survival prognostic model for stage III hepatocellular carcinoma: a real-world, multicenter clinical study.

OBJECTIVE: To construct a survival prediction model for patients with TNM stage III hepatocellular carcinoma (HCC) to guide the clinical diagnosis and treatment of HCC patients and improve prognosis. METHODS: Based on data from patients with stage III (AJCC 7th TNM stage) recorded by the American Institute of Cancer Research from 2010 to 2013, risk factors affecting the prognosis were screened by Cox univariate and multivariate regression, line plots was constructed, and the credibility of the model was verified by Boostrap method. ROC operating curves, calibration curves and DCA clinical decision curves were used to evaluate the model, and Kaplan-Meier was used for survival analysis was used to evaluate the efficacy of the model. External survival data from patients newly diagnosed with stage III hepatocellular carcinoma during 2014-2015 were used to validate and fit the model and to optimize the model. RESULTS: Age > 75 years vs.18-53 years [HR = 1.502; 95%CI(1.134-1.990)], stage IIIC vs. Stage IIIA [HR = 1.930; 95%CI(1.509-2.470)], lobotomy vs. non-surgery [HR = 0.295; 95%CI(0.228-0.383)], radiotherapy vs. non-radiotherapy [HR = 0.481; 95%CI(0.373-0.619)], chemotherapy vs. Non-chemotherapy [HR = 0.443; 95%CI(0.381-0.515)], positive serum AFP before treatment vs. negative [HR = 1.667; 95%CI(1.356-2.049)], the above indicators are independent prognostic factors for patients with stage III hepatocellular carcinoma, and the P values for the above results were less than 0.05. A joint prediction model was constructed based on age, TNM stage, whether and how to operate, whether to receive radiotherapy, whether to receive chemotherapy, pre-treatment serum AFP status and liver fibrosis score. The consistency index of the improved prognosis model was 0.725. CONCLUSIONS: The traditional TNM staging has limitations for clinical diagnosis and treatment, while the Nomogram model modified by TNM staging has good predictive efficacy and clinical significance.

A dramatic decline in fruit citrate induced by mutagenesis of a NAC transcription factor, AcNAC1.

Citrate is a common primary metabolite which often characterizes fruit flavour. The key regulators of citrate accumulation in fruit and vegetables are poorly understood. We systematically analysed the dynamic profiles of organic acid components during the development of kiwifruit (Actinidia spp.). Citrate continuously accumulated so that it became the predominate contributor to total acidity at harvest. Based on a co-expression network analysis using different kiwifruit cultivars, an Al-ACTIVATED MALATE TRANSPORTER gene (AcALMT1) was identified as a candidate responsible for citrate accumulation. Electrophysiological assays using expression of this gene in Xenopus oocytes revealed that AcALMT1 functions as a citrate transporter. Additionally, transient overexpression of AcALMT1 in kiwifruit significantly increased citrate content, while tissues showing higher AcALMT1 expression accumulated more citrate. The expression of AcALMT1 was highly correlated with 17 transcription factor candidates. However, dual-luciferase and EMSA assays indicated that only the NAC transcription factor, AcNAC1, activated AcALMT1 expression via direct binding to its promoter. Targeted CRISPR-Cas9-induced mutagenesis of AcNAC1 in kiwifruit resulted in dramatic declines in citrate levels while malate and quinate levels were not substantially affected. Our findings show that transcriptional regulation of a major citrate transporter, by a NAC transcription factor, is responsible for citrate accumulation in kiwifruit, which has broad implications for other fruits and vegetables.

Switchable optical ring lattice in free space.

Optical lattices with spatially regular structures have recently attracted considerable attention across physics and optics communities. In particular, due to the increasing emergence of new structured light fields, diverse lattices with rich topology are being generated via multi-beam interference. Here, we report a specific ring lattice with radial lobe structures generated via superposition of two ring Airy vortex beams (RAVBs). We show that the lattice morphology evolves upon propagation in free space, switching from a bright-ring lattice to dark-ring lattice and even to fascinating multilayer texture. This underlying physical mechanism is related to the variation of the unique intermodal phase between the RAVBs as well as topological energy flow with symmetry breaking. Our finds provide an approach for engineering customized ring lattices to inspire a wide variety of new applications.

Experimental Study on Repairing Peripheral Nerve Defects with Novel Bionic Tissue Engineering.

Peripheral nerve defects are a worldwide problem, and autologous nerve transplantation is currently the gold-standard treatment for them. Tissue-engineered nerve (TEN) grafts are widely considered promising methods for the same, and have attracted much attention. To improve repair, the incorporation of bionics into TEN grafts has become a focus of research. In this study, a novel bionic TEN graft with a biomimetic structure and composition is designed. For this purpose, a chitin helical scaffold is fabricated by means of mold casting and acetylation using chitosan as the raw material, following which a fibrous membrane is electrospun on the outer layer of the chitin scaffold. The lumen of the structure is filled with human bone mesenchymal stem cell-derived extracellular matrix and fibers to provide nutrition and topographic guidance, respectively. The prepared TEN graft is then transplanted to bridge 10 mm sciatic nerve defects in rats. Morphological and functional examination shows that the repair effects of the TEN grafts and autografts are similar. The bionic TEN graft described in this study shows great potential for application and offers a new way to repair clinical peripheral nerve defects.

Sublethal effects of an indoxacarb enantiomer insecticide on Plutella xylostella caterpillar and Chrysoperla sinica predator.

Plutella xylostella (L.) is a migratory species and an important insect pest of cruciferous crops worldwide, and Chrysoperla sinica (Tjeder) is a predaceous insect of agricultural and forest pests in the field. Indoxacarb has two enantiomers: (+)-S-indoxacarb and (-)-R-indoxacarb. This study was conducted to clarify the selective toxicity and sublethal effects of both enantiomers on P. xylostella and C. sinica. The (+)-S-indoxacarb isomer had greater acute toxicity to P. xylostella and C. sinica, while (-)-R-indoxacarb had less toxicity to P. xylostella and low toxicity to C. sinica. Lethal concentration 25 % (LC25) of (+)-S-indoxacarb had significant effects on the development, population, and fecundity of P. xylostella and C. sinica. The LC25 concentration of (-)-R-indoxacarb had a significant effect on the oviposition of P. xylostella. The field recommended concentration of (-)-R-indoxacarb significantly affected the pupal stage, adult survival rate, oviposition, and larval survival rate of C. sinica. Both enantiomers could significantly affect the search efficiency, successful attack rate, prey handling time, and maximum predation of C. sinica larvae, and the effects of (+)-S-indoxacarb alone were greater than those of (-)-R-indoxacarb. This study provided evidence of the different selective toxicity, sublethal effects of indoxacarb enantiomers on P. xylostella and C. sinica, which of the results could provide a basis for more rational use of indoxacarb in ecosystems.

Medicine+information: Exploring patent applications in precision therapy in cardiac surgery / 中国胸心血管外科临床杂志

@#Currently, in precision cardiac surgery, there are still some pressing issues that need to be addressed. For example, cardiopulmonary bypass remains a critical factor in precise surgical treatment, and many core aspects still rely on the experience and subjective judgment of cardiopulmonary bypass specialists and surgeons, lacking precise data feedback. With the increasing elderly population and rising surgical complexity, precise feedback during cardiopulmonary bypass becomes crucial for improving surgical success rates and facilitating high-complexity procedures. Overcoming these key challenges requires not only a solid medical background but also close collaboration among multiple interdisciplinary fields. Establishing a multidisciplinary team encompassing professionals from the medical, information, software, and related industries can provide high-quality solutions to these challenges. This article shows several patents from a collaborative medical and electronic information team, illustrating how to identify unresolved technical issues and find corresponding solutions in the field of precision cardiac surgery while sharing experiences in applying for invention patents.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

Prevalence, patterns and prognosis of multimorbidity among middle-aged and elderly inpatients with chronic obstructive pulmonary disease / 中华预防医学杂志

Objective: To explore the characteristics, patterns of multimorbidity and the impact on quality of life and the prognosis of middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD). Methods: This is a cross-sectional study. From January 2012 to December 2021, 939 middle-aged and elderly COPD patients hospitalized in Beijing Hospital were selected by the convenient sampling method. The basic data of patients and the date of 16 common chronic diseases were collected. Patterns of multimorbidity were depicted by cluster analysis. Generalized linear regression model and logistic regression were used to evaluate the multimorbidity patterns and their prognosis. Results: At least one multimorbidity existed among 93.40% of COPD patients, and the median number of multimorbidity was 3. The top five multimorbidity among the patients were hypertension (57.93%, 544/939), coronary heart disease (33.76%,317/939), heart failure (31.95%,300/939), hyperlipidemia (31.63%,297/939) and arrhythmia (27.37%,257/939). Four multimorbidity patterns were identified, cardiometabolic and metabolic multimorbidity, kidney disease multimorbidity, respiratory-digestive-tumor multimorbidity and other multimorbidity. Cardiometabolic and metabolic multimorbidity was most common (590/939, 62.83%). Compared with non-cardiometabolic and metabolic multimorbidity, the incharge ADL score of patients with this multimorbidity decreased by 7 points (95%CI:-11.22- -3.34), Correspondingly, patients with kidney disease multimorbidity decreased by 14 points (95%CI:-24.12- -3.30) on the incharge score. The presence or absence of kidney disease multimorbidity had the greatest impact on discharge score, which was reduced by 12 points in comparison with patients without this multimorbidity (95%CI:-22.43- -2.40). ICU admission is mostly affected by the presence of cardiometabolic and metabolic multimorbidity (OR=2.44, 95%CI: 1.51-3.92) and kidney disease multimorbidity (OR=2.58, 95%CI: 1.01-6.60). The risk of death is the highest for cardiometabolic and metabolic multimorbidity (OR=2.24, 95%CI: 1.19-4.21). Conclusion: Multimorbidity is common in COPD patients. The most common pattern is cardiometabolic and metabolic multimorbidity. Cardiometabolic and metabolic multimorbidity and kidney disease multimorbidity significantly affect the quality of life and often associate with a poor prognosis.

Research on classification of Korotkoff sounds phases based on deep learning / 中国胸心血管外科临床杂志

@#Objective     To recognize the different phases of Korotkoff sounds through deep learning technology, so as to improve the accuracy of blood pressure measurement in different populations. Methods     A classification model of the Korotkoff sounds phases was designed, which fused attention mechanism (Attention), residual network (ResNet) and bidirectional long short-term memory (BiLSTM). First, a single Korotkoff sound signal was extracted from the whole Korotkoff sounds signals beat by beat, and each Korotkoff sound signal was converted into a Mel spectrogram. Then, the local feature extraction of Mel spectrogram was processed by using the Attention mechanism and ResNet network, and BiLSTM network was used to deal with the temporal relations between features, and full-connection layer network was applied in reducing the dimension of features. Finally, the classification was completed by SoftMax function. The dataset used in this study was collected from 44 volunteers (24 females, 20 males with an average age of 36 years), and the model performance was verified using 10-fold cross-validation. Results     The classification accuracy of the established model for the 5 types of Korotkoff sounds phases was 93.4%, which was higher than that of other models. Conclusion     This study proves that the deep learning method can accurately classify Korotkoff sounds phases, which lays a strong technical foundation for the subsequent design of automatic blood pressure measurement methods based on the classification of the Korotkoff sounds phases.

Exogenous γ-Aminobutyric Acid Can Improve Seed Germination and Seedling Growth of Two Cotton Cultivars under Salt Stress.

Excessive salt content in soil has adverse effects on cotton production, especially during the germination and seedling stages. γ-aminobutyric acid (GABA) is an important active substance that is expected to improve the resistance of plants to abiotic stresses. This study focused on two cotton cultivars (Gossypium hirsutum L.: Tahe 2 and Xinluzhong 62) and investigated the impact of exogenous GABA (0, 1, 2, 3, and 4 mM) on seed germination, seedling growth, and related morphological, physiological, and biochemical indicators under salt stress (150 mM NaCl). The results showed that salt stress significantly reduced the germination rate and germination index of cotton seeds (decreased by 20.34% and 32.14% for Tahe 2 and Xinluzhong 62, respectively), leading to decreased seedling height and biomass and causing leaf yellowing. Salt stress induced osmotic stress in seedlings, resulting in ion imbalance (marked reduction in K+/Na+ ratio) and oxidative damage. Under salt stress conditions, exogenous GABA increased the germination rate (increased by 10.64~23.40% and 2.63~31.58% for Tahe 2 and Xinluzhong 62, respectively) and germination index of cotton seeds, as well as plant height and biomass. GABA treatment improved leaf yellowing. Exogenous GABA treatment increased the content of proline and soluble sugars, with varying effects on betaine. Exogenous GABA treatment reduced the Na+ content in seedlings, increased the K+ content, and increased the K+/Na+ ratio (increased by 20.44~28.08% and 29.54~76.33% for Tahe 2 and Xinluzhong 62, respectively). Exogenous GABA treatment enhanced the activities of superoxide dismutase and peroxidase, and reduced the accumulation of hydrogen peroxide and malondialdehyde, but had a negative impact on catalase activity. In conclusion, exogenous GABA effectively improved cotton seed germination. By regulating osmoprotectant levels, maintaining ion homeostasis, and alleviating oxidative stress, GABA mitigated the adverse effects of salt stress on cotton seedling growth.

Targeting disordered-structured domain interactions in Galectin-3 based on NMR and enhanced MD.

Intrinsically disordered regions (IDRs) are common and important functional domains in many proteins. However, IDRs are difficult to target for drug development due to the lack of defined structures that would facilitate the identification of possible drug-binding pockets. Galectin-3 is a carbohydrate-binding protein of which overexpression has been implicated in a wide variety of disorders, including cancer and inflammation. Apart from its carbohydrate-recognition/binding domain (CRD), Galectin-3 also contains a functionally important disordered N-terminal domain (NTD) that contacts the C-terminal domain (CTD) and could be a target for drug development. To overcome challenges involved in inhibitor design due to lack of structure and the highly dynamic nature of the NTD, we used a protocol combining nuclear magnetic resonance data from recombinant Galectin-3 with accelerated molecular dynamics (MD) simulations. This approach identified a pocket in the CTD with which the NTD makes frequent contact. In accordance with this model, mutation of residues L131 and L203 in this pocket caused loss of Galectin-3 agglutination ability, signifying the functional relevance of the cavity. In silico screening was used to design candidate inhibitory peptides targeting the newly discovered cavity, and experimental testing of only three of these yielded one peptide that inhibits the agglutination promoted by wild-type Galectin-3. NMR experiments further confirmed that this peptide indeed binds to a cavity in the CTD, not within the actual CRD. Our results show that it is possible to apply a combination of MD simulations and NMR experiments to precisely predict the binding interface of a disordered domain with a structured domain, and furthermore use this predicted interface for designing inhibitors. This procedure can potentially be extended to many other targets in which similar IDR interactions play a vital functional role.