Unraveling a Small Secreted Peptide SUBPEP3 That Positively Regulates Salt-Stress Tolerance in Pyrus betulifolia.

Small secreted peptides (SSPs) play important roles in regulating plants' growth and development in response to external stimulus, but the genes and functions of SSPs in many species are still unknown. Therefore, it is particularly significant to characterize and annotate SSP genes in plant genomes. As a widely used stock of pears, Pyrus betulifolia has strong resistance to biotic and abiotic stresses. In this study, we analyzed the SSPs genes in the genome of P. betulifolia according to their characteristics and homology. A total of 1195 SSP genes were identified, and most of them are signaling molecules. Among these, we identified a new SSP, subtilase peptide 3 (SUBPEP3), which derived from the PA region of preSUBPEP3, increasing the expression level under salt stress. Both adding synthetic peptide SUBPEP3 to the culture medium of pears and the overexpression of SUBPEP3 in tobacco can improve the salt tolerance of plants. In summary, we annotated the SSP genes in the P. betulifolia genome and identified a small secreted peptide SUBPEP3 that regulates the salt tolerance of P. betulifolia, which provides an important theoretical basis for further revealing the function of SSPs.

Interictal interleukin-6 and tumor necrosis factor α levels are associated with seizure recurrence in adults with epilepsy.

BACKGROUND: Although there are models predicting epilepsy recurrence under different clinical conditions, few studies have examined blood biomarkers. Inflammation plays a crucial role in the occurrence and development of epilepsy. We analyzed inflammatory mediators in a regional hospital-based epilepsy cohort and investigated their relationship with subsequent epilepsy recurrence. METHODS: Interictal inflammatory mediators were measured in 128 patients diagnosed with epilepsy participating in a prospective study. Inflammatory mediators were compared during the follow-up period between patients who experienced epilepsy recurrence and those who did not. We also assessed the correlation between inflammatory mediators and the time interval until the next recurrence. RESULTS: Over a median 4-month follow-up period, 41 patients experienced seizure recurrence. Differences in interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels were observed between seizure recurrence and non-recurrence groups. After adjusting for covariates through multivariate Cox regression analysis, the patients in the third IL-6 tertile (>2.31 pg/mL; HR: 2.49; 95 % CI: 1.00-6.16; P = 0.049) and in the third TNF-α tertile (>0.74 pg/mL; HR: 2.80; 95 % CI: 1.13-6.92; P = 0.026) had higher risk of seizure recurrence. The time until the next recurrence was negatively correlated with IL-6 level (ρ =  - 0.392, P = 0.011). CONCLUSION: High levels of IL-6 and TNF-α are associated with a higher possibility of seizure recurrence. Future predictive models should also include inflammatory mediators in addition to clinical variables.

Bronchial thermoplasty decreases airway remodeling by inhibiting autophagy via the AMPK/mTOR signaling pathway.

Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Age and sex estimation in cephalometric radiographs based on multitask convolutional neural networks.

OBJECTIVES: Age and sex characteristics are evident in cephalometric radiographs (CRs), yet their accurate estimation remains challenging due to the complexity of these images. This study aimed to harness deep learning to automate age and sex estimation from CRs, potentially simplifying their interpretation. STUDY DESIGN: We compared the performance of 4 deep learning models (SVM, R-net, VGG16-SingleTask, and our proposed VGG16-MultiTask) in estimating age and sex from the testing dataset, utilizing a VGG16-based multitask deep learning model on 4,557 CRs. Gradient-weighted class activation mapping (Grad-CAM) was incorporated to identify sex. Performance was assessed using mean absolute error (MAE), specificity, sensitivity, F1 score, and the area under the curve (AUC) in receiver operating characteristic analysis. RESULTS: The VGG16-MultiTask model outperformed the others, with the lowest MAE (0.864±1.602) and highest sensitivity (0.85), specificity (0.88), F1 score (0.863), and AUC (0.93), demonstrating superior efficacy and robust performance. CONCLUSIONS: The VGG multitask model demonstrates significant potential in enhancing age and sex estimation from cephalometric analysis, underscoring the role of AI in improving biomedical interpretations.

Additive-free oxychlorination of unsaturated C-C bonds with tert-butyl hypochlorite and water.

Herein we report an additive-free protocol for the facile synthesis of α,α-dichloroketones and α-chlorohydrins from various aryl terminal, diaryl internal, and aliphatic terminal alkynes and alkenes, respectively. The commercially available tert-butyl hypochlorite (tBuOCl) was employed as a suitable chlorinating reagent, being accompanied by the less harmful tBuOH as the by-product. In addition, the oxygen atoms in the products came from water rather than molecular oxygen, based on the 18O-labelling experiments. Meanwhile, the diastereoselectivity of the Z- and the corresponding E-alkenes has been compared and rationalized. Using a group of control experiments, the possible mechanisms have been proposed as the initial electrophilic chlorination of unsaturated C-C bonds in a Markovnikov-addition manner in general followed by a nucleophilic addition with water. This work simplified the oxychlorination method with a mild chlorine source and a green oxygen source under ambient conditions.

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state.

PURPOSE: Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models. METHODS: The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by H2O2 and treated using DOP. CCK-8 and EdU were carried out to detect cell proliferation. ELISA, qRT-PCR, and Western blot were conducted to measure the expression of pro-inflammatory cytokines IL17A, IL-23, IL1ß, tumor necrosis factor alpha (TNF-α), and IL-6. Reactive oxygen species (ROS) level in keratinocytes was detected by flow cytometry. Cell proliferation-associated proteins (PCNA, Ki67, Cyclin D1) and pathway proteins (p-AKT and AKT), and oxidative stress marker proteins (Nrf-2, CAT, SOD1) were detected by Western blot. RESULT: DOP did not affect the proliferation of normal keratinocytes, but DOP was able to inhibit the proliferative activity of IL-22-induced overproliferating keratinocytes and suppress the expression of proliferation-related factors PCNA, Ki67, and Cyclin D1 as well as the proliferation pathway p-AKT. In addition, DOP treatment was able to inhibit IL-22 and LPS-induced inflammation and H2O2-induced oxidative stress, including the expression of IL17A, IL-23, IL1ß, TNF-α, IL-6, and IL1ß, as well as the expression levels of intracellular ROS levels and cellular oxidative stress-related indicators SOD, MDA, CAT, Nrf-2 and SOD1. CONCLUSION: DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.

Edaravone dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration.

Poststroke inflammation is essential in the mechanism of secondary injury, and it is orchestrated by resident microglia, astrocytes, and circulating immune cells. Edaravone dexborneol (EDB) is a combination of edaravone and borneol that has been identified as a clinical protectant for stroke management. In this study, we verified the anti-inflammatory effect of EDB in the mouse model of ischemia and investigated its modulatory action on inflammation-related cells. C57BL/6 male mice, which had the transient middle cerebral artery occlusion (tMCAO), were treated (i.p.) with EDB (15 mg/kg). EDB administration significantly reduced the brain infarction and improved the sensorimotor function after stroke. And EDB alleviated the neuroinflammation by restraining the polarization of microglia/macrophages and astrocyte toward proinflammatory phenotype and inhibiting the production of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6) and chemokines (including MCP-1 and CXCL1). Furthermore, EDB ameliorated the MCAO-induced impairment of Blood-brain barrier (BBB) by suppressing the degradation of tight junction protein and attenuated the accumulation of peripheral leukocytes in the ischemic brain. Additionally, systemic EDB administration inhibited the macrophage phenotypic shift toward the M1 phenotype and the macrophage-dependent inflammatory response in the spleen and blood. Collectively, EDB protects against ischemic stroke injury by inhibiting the proinflammatory activation of microglia/macrophages and astrocytes and through reduction by invasion of circulating immune cells, which reduces central and peripheral inflammation following stroke.

Coexistence of a novel SRBD1-ALK, ALK-CACNA1D double-fusion in a lung adenocarcinoma patient and response to alectinib: A case report.

A Chinese male patient with advanced lung adenocarcinoma experienced disease progression one and a half years after receiving first-line immunochemotherapy. The second biopsy was performed and tissue immunohistochemistry revealed Anaplastic lymphoma kinase (ALK) expression in the cytoplasm of tumor cells, so he began to receive Alectinib treatment. Then the next generation sequencing found double fusion variants of S1 RNA binding domain 1 (SRBD1)- ALK and ALK- Calcium voltage-gated channel subunit alpha1 D (CACNA1D). After continuous Alectinib treatment for 7 months, almost complete response (CR) was achieved. The patient is currently taking Alectinib for 13 months, the condition is stable, and is waiting for the next cycle of efficacy evaluation.

Construction of an immune-related risk score signature for gastric cancer based on multi-omics data.

Early identification of gastric cancer (GC) is associated with a superior survival rate compared to advanced GC. However, the poor specificity and sensitivity of traditional biomarkers suggest the importance of identifying more effective biomarkers. This study aimed to identify novel biomarkers for the prognosis of GC and construct a risk score (RS) signature based on these biomarkers, with to validation of its predictive performance. We used multi-omics data from The Cancer Genome Atlas to analyze the significance of differences in each omics data and combined the data using Fisher's method. Hub genes were subsequently subjected to univariate Cox and LASSO regression analyses and used to construct the RS signature. The RS of each patient was calculated, and the patients were divided into two subgroups according to the RS. The RS signature was validated in two independent datasets from the Gene Expression Omnibus and subsequent analyses were subsequently conducted. Five immune-related genes strongly linked to the prognosis of GC patients were obtained, namely CGB5, SLC10A2, THPO, PDGFRB, and APOD. The results revealed significant differences in overall survival between the two subgroups (p < 0.001) and indicated the high accuracy of the RS signature. When validated in two independent datasets, the results were consistent with those in the training dataset (p = 0.003 and p = 0.001). Subsequent analyses revealed that the RS signature is independent and has broad applicability among various GC subtypes. In conclusion, we used multi-omics data to obtain five immune-related genes comprising the RS signature, which can independently and effectively predict the prognosis of GC patients with high accuracy.

An interactive nuclei segmentation framework with Voronoi diagrams and weighted convex difference for cervical cancer pathology images.

Objective.Nuclei segmentation is crucial for pathologists to accurately classify and grade cancer. However, this process faces significant challenges, such as the complex background structures in pathological images, the high-density distribution of nuclei, and cell adhesion.Approach.In this paper, we present an interactive nuclei segmentation framework that increases the precision of nuclei segmentation. Our framework incorporates expert monitoring to gather as much prior information as possible and accurately segment complex nucleus images through limited pathologist interaction, where only a small portion of the nucleus locations in each image are labeled. The initial contour is determined by the Voronoi diagram generated from the labeled points, which is then input into an optimized weighted convex difference model to regularize partition boundaries in an image. Specifically, we provide theoretical proof of the mathematical model, stating that the objective function monotonically decreases. Furthermore, we explore a postprocessing stage that incorporates histograms, which are simple and easy to handle and prevent arbitrariness and subjectivity in individual choices.Main results.To evaluate our approach, we conduct experiments on both a cervical cancer dataset and a nasopharyngeal cancer dataset. The experimental results demonstrate that our approach achieves competitive performance compared to other methods.Significance.The Voronoi diagram in the paper serves as prior information for the active contour, providing positional information for individual cells. Moreover, the active contour model achieves precise segmentation results while offering mathematical interpretability.

Photodynamic therapy for treatment of recurrent hemoptysis secondary to pulmonary endometriosis: a case report.

Pulmonary endometriosis (PEM) is rare, and drug therapy remains the primary treatment. However, patients with PEM frequently experience recurrent hemoptysis that is refractory to pharmacological intervention. We herein describe a patient with PEM who developed recurrent hemoptysis and was successfully treated with photodynamic therapy (PDT) after drug withdrawal. The patient was admitted to our hospital because of recurrent hemoptysis despite repeated drug treatments for more than 1 year. Given that PDT targets specific tissues and destroys vascular endothelial cells through the cytotoxic effect produced by the photodynamic reaction of the photosensitizer, we considered that it may effectively control hemoptysis secondary to vascular morphological changes in PEM. Therefore, we performed PDT in this case, and the patient's recurrent hemoptysis regressed. Approximately 2 years following PDT, the patient had recovered well and reported no discomfort. We recommend consideration of PDT as a treatment option for patients with PEM who develop recurrent hemoptysis after drug withdrawal. Notably, the patient's lung lesions should be superficial and limited, and no contraindications should be present.

Association of Malnutrition Diagnosed Using Global Leadership Initiative on Malnutrition Criteria with Severe Postoperative Complications After Gastrectomy in Patients with Gastric Cancer.

Background: The purpose of this study was to investigate the relationship between malnutrition assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria and the occurrence of severe postoperative complications (SPCs) after gastrectomy in patients with gastric cancer. Methods: A total of 220 patients with gastric cancer were included in this retrospective study. According to the GLIM criteria, the first step was to use the Nutrition Risk Screening Score 2002 to conduct nutritional risk screening for patients and the second step was to diagnose and grade the severity of malnutrition in patients at risk of malnutrition. According to the Clavien-Dindo classification system, SPCs were defined as C-D Grade IIIa or higher. Results: Overall, 66 (30.0%) patients were diagnosed with malnutrition, including 32 (14.5%) with moderate malnutrition and 34 (15.5%) with severe malnutrition. The incidence of SPCs was 14.5%, and the most frequent postoperative event was anastomotic leakage. In the multivariate regression analysis, malnutrition was considered an independent risk factor for SPCs (P < .001). After adjusting for various factors, the grading association remained statistically significant. Compared with patients with normal nutrition, patients with moderate and severe malnutrition have a nearly 15-fold (OR = 15.682, 95% CI: 4.481-54.877, P < .001) and 20-fold (OR = 20.554, 95% CI: 5.771-73.202, P < .001) increased risk of developing SPCs, respectively. Conclusions: Malnutrition assessed by GLIM was an independent risk factor for SPCs in gastric cancer patients. Therefore, early identification of malnourished patients is crucial for timely implementation of nutritional treatment and reducing the occurrence of postoperative complications.

The optimal intravesical maintenance chemotherapy scheme for the intermediate-risk group non-muscle-invasive bladder cancer.

OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

Role of immunophenotypic characterisation in prognostic subtyping of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is classified by the 5th WHO classification of tumours of the digestive system as large duct type (LDT) and small duct type (SDT), based on the anatomical location, morphological appearances, immunophenotype, and gene events. We evaluated the subtyping system using real-world data and established a supplementary method using immunohistochemical (IHC) detection. We retrospectively investigated 190 cases of surgically resected iCCA and classified them according to histological evaluations and gene detection. The prognostic value of the IHC markers were evaluated according to the relapse-free survival (RFS) and overall survival (OS). Basic histological classification was insufficient, with 61 cases classified as uncertain. This method showed no prognostic value for RFS or OS. The four-marker IHC detection, including EMA, S100P, N-cadherin, and CRP, which classified 68 cases as LDT, 108 cases as SDT, and 14 cases as uncertain, was highly efficient in subtyping and prognosis. The seven-marker method, including CD56, MUC5AC and MUC6, was consistent with the four-marker method. FGFR2 gene fusion was exclusively detected in 20 cases of SDT iCCA, according to the four- and seven-marker IHC detection. This novel method of iCCA classification exhibited diagnostic, prognostic and therapeutic value in clinical practice.

Exploring the Causality Between Plasma Brain-Derived Neurotrophic Factor and Neurological Diseases: A Mendelian Randomization Study.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a protein synthesized in the brain and widely expressed in the nervous system. Previous studies have demonstrated a controversial role of BDNF in neurological diseases. OBJECTIVE: In this study, we aimed to assess the association between BDNF levels and the risk of neurological diseases by Mendelian randomization analysis. METHODS: From a genome-wide association analysis of plasma proteins comprising 3,301 European participants, we isolated 25 genetic variations as instrumental variables for BDNF levels. Summary statistics data on six common neurological diseases as outcome variables. Two-sample Mendelian randomization (MR) analysis was used to assess whether plasma BDNF is causally related to neurological diseases. We also performed sensitivity analysis to ensure the robustness of the results and reverse MR to exclude potential reverse causality. RESULTS: We confirmed the significant causal relationship between BDNF levels and the risk of Alzheimer's disease (AD) (OR, 0.92; 95% CI, 0.85, 0.98; p = 0.013). Other methods have also shown similar results. We infer that BDNF also reduces the risk of epilepsy (OR, 0.94; 95% CI, 0.90, 0.98; p = 0.004). In reverse MR analysis, we also found that AD can affect the level of BDNF. CONCLUSIONS: Our study suggests higher plasma BDNF was associated with the reduced risk of AD. Moreover, higher plasma BDNF is a protective factor on AD and focal epilepsy. The results provide credence to the idea that BDNF may play a significant role in the development of focal epilepsy and AD.

CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.

Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.

Research on the effectiveness and safety of bronchial thermoplasty in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To investigate the clinical efficacy and safety of bronchial thermoplasty (BT) in treating patients with chronic obstructive pulmonary disease (COPD). METHODS: Clinical data of 57 COPD patients were randomized into the control (n = 29, conventional inhalation therapy) or intervention group (n = 28, conventional inhalation therapy plus BT). Primary outcomes were differences in clinical symptom changes, pulmonary function-related indicators, modified Medical Research Council (mMRC), 6-min walk test (6MWT), COPD assessment test (CAT) score and acute exacerbation incidence from baseline to an average of 3 and 12 months. Safety was assessed by adverse events. RESULTS: FEV1, FEV1(%, predicted) and FVC in both groups improved to varying degrees post-treatment compared with those pre-treatment (P < 0.05). The Intervention group showed greater improving amplitudes of FEV1 (Ftime × between groups = 21.713, P < 0.001) and FEV1(%, predicted) (Ftime × between groups = 31.216, P < 0.001) than the control group, and there was no significant difference in FVC variation trend (Ftime × between groups = 1.705, P = 0.193). mMRC, 6MWT and CAT scores of both groups post-treatment improved to varying degrees (Ps < 0.05), but the improving amplitudes of mMRC (Ftime × between groups = 3.947, P = 0.025), 6MWT (Ftime × between groups = 16.988, P < 0.001) and CAT score (Ftime × between groups = 16.741, P < 0.001) in the intervention group were greater than the control group. According to risk assessment of COPD acute exacerbation, the proportion of high-risk COPD patients with acute exacerbation in the control and intervention groups at 1 year post-treatment (100% vs 65%, 100% vs 28.6%), inpatient proportion (100% vs 62.1%; 100% vs 28.6%), COPD acute exacerbations [3.0 (2.50, 5.0) vs 1.0 (1.0, 2.50); 3.0(3.0, 4.0) vs 0 (0, 1.0)] and hospitalizations [2.0 (2.0, 3.0) vs 1.0 (0, 2.0); 2.0 (2.0, 3.0) vs 0 (0, 1.0)] were significantly lower than those pre-treatment (P < 0.05). Besides, data of the intervention group were significantly lower than the control group at each timepoint after treatment (P < 0.05). CONCLUSIONS: Combined BT therapy is superior to conventional medical treatment in improving lung function and quality of life of COPD patients, and it also significantly reduces the COPD exacerbation risk without causing serious adverse events.