Redox-sensitive cysteine(RSC)thiol plays an important role in many biological processes such as photosynthesis,cellular metabolism,and transcription.Therefore,it is necessary to identify red-ox-sensitive cysteine accurately.However,traditional redox-sensitive cysteine identification is very ex-pensive and time-consuming.At present,there is an urgent need for a mathematical calculation method to identify sequence information and redox-sensitive cysteines quickly and accurately.Here,we devel-oped an effective predictor called iRSC-PseAAC,which used the dimension reduction algorithm LDA combined with the support vector machine to predict redox-sensitive cysteine sites.In the cross-validation results,the specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.841,0.868,0.859 and 0.692 respectively.In the independent dataset results,the Sp,Sn,Acc and MCC were 0.906,0.882,0.890 and 0.767 respectively.compared with existing prediction methods,iRSC-PseAAC had obvious improvement effect.The method proposed for this study can also be used for many problems in computational proteomics.

ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients， construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7：3. For the modelling group， LASSO regression was applied to screen variables and select predictors， and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve （AUC）， and in addition， calibration analysis and decision curve analysis （DCA） were performed on the model. ResultsLASSO regression identified 14 potential predictive factors， and further logistic regression analysis showed that hepatic injury， surgery， anemia， hypoalbuminemia， illness course， invasive operation， hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables， with an AUC95%CI of 0.980 （0.973， 0.896） for the training set and an AUC95%CI of 0.956 （0.795， 1.000） for internal validation， indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line， and the decision curve analysis （DCA） showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

OBJECTIVE: To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation. METHODS: Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot. RESULTS: The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2. CONCLUSION The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.
Codon, Nonsense ; Factor IX/metabolism* ; HeLa Cells ; Humans ; Mutation ; RNA Splicing ; RNA, Messenger/metabolism*

OBJECTIVE: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC. METHODS: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs. RESULTS: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05). CONCLUSION The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

In December 2019, coronavirus disease 2019 (COVID-19), a new de novo infectious disease, was first identified in Wuhan, China and quickly spread across China and around the world. The etiology was a novel betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Lu et al., 2020). On Mar. 11, 2020, World Health Organization (WHO) characterized COVID-19 as a global pandemic. As of Mar. 22, 2020, over 292 000 confirmed COVID-19 cases have been reported globally. To date, COVID-19, with its high infectivity, has killed more people than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) combined (Wu and McGoogan, 2020).
Adult ; Betacoronavirus ; COVID-19 ; COVID-19 Testing ; China ; Clinical Laboratory Techniques ; Coronavirus Infections/diagnostic imaging* ; Female ; Fever/virology* ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/diagnostic imaging* ; Radiography, Thoracic ; SARS-CoV-2 ; Tomography, X-Ray Computed ; Treatment Outcome

Objective To analyze the resistance of influenza virus to neuraminidase inhibitors (NAI) in Henan province during 2017-2018. Methods Virus were collected from the Henan Influenza Surveillance Network during 2017-2018. 36 confirmed influenza virus(with 15 H1pdm09，6 H3N2 and 15 B) were selected to test resistance to oseltamivir and zanamivi with fluorescence(FL). The NAI sensitive reference viruses were A/California/12/2012(H1pdm09)-275H,A/Beijing Haidian/1942/2014(H3N2)-119E and B/Rochester/02/2001-198D. The NAI resistant reference viruses were A/ Texas/23/2012(H1pdm9)-H275Y, A/Texas/12/2007(H3N2)-E119V and B/Rochester/02/2001-D198N. Results The half maximal inhibitory concentration(IC50) of A/California/12/2012(H1pdm09)-275H, A/Beijing-Haidian/1942/2014(H3N2)-119E and B/Rochester/02/2001-198D for oseltamivir were 0.29 nmol/L (nM),0.10 nM and 12.71 nM, and for zanamivir were 0.2 nM, 0.49 nM and 0.33 nM respectively. The IC50 for oxastatin of H1pdm09 and H3N2 ranged from (0.28-1.37 nM) and (0.08-0.17 nM) respectively, the IC50 for zanamivir ranged from (0.15-0.49 nM) and (0.12-0.22 nM), all was within 10 fold IC50 of the reference virus(corresponding type); the IC50 value of type B for oseltamivir and zanamivir ranged from (11.83-24.59 nM) and (0.48-1.25 nM), all was within 5 fold IC50 of the reference virus. Conclusion All the tested influenza strains isolated in Henan province during 2017-2018 were sensitive to NAI.

Adult ; Aged ; Brain ; diagnostic imaging ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Optic Neuropathy, Ischemic ; diagnostic imaging ; physiopathology