Clinical characteristics and risk factors in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.

Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.

The clinical characteristics of COVID-19 omicron variant infection in pregnant women and their neonates.

Objective: The objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China. Methods: The clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay. Results: Seventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment. Conclusion: Although preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians.

Combining the Real-Time Vial Sharing Strategy with Daily-Rate Charge Mode for Antimicrobial Drugs of Inpatients: An Economical and Practical Method for Patients and Hospitals.

Background: Antimicrobial agents' wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients' families. Moreover, the cost of disposing of antimicrobial agents' waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients' expenditures, saving medical costs, and reducing drug proportion. Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children's Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed. Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499. Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients' payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.

Etiology analysis and G6PD deficiency for term infants with jaundice in Yangjiang of western Guangdong.

Objective: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of this study is to evaluate the risk factors associated with hyperbilirubinemia in infants from the western part of Guangdong Province, and to assess the contribution of G6PD deficiency to neonatal jaundice. Methods: The term infants with neonatal hyperbilirubinemia in People's Hospital of Yangjiang from June 2018 to July 2022 were recruited for the retrospective analysis. All the infants underwent quantitative detection of the G6PD enzyme. The etiology was determined through laboratory tests and clinical manifestations. Results: Out of 1,119 term infants, 435 cases presented with jaundice. For the etiology analysis, infection was responsible for 16.09% (70/435), G6PD deficiency accounted for 9.66% (42/435), of which 3 were complicated with acute bilirubin encephalopathy), bleeding accounted for 8.05% (35/435), hemolytic diseases accounted for 3.45% (15/435), and breast milk jaundice accounted for 2.53% (11/435). One case (0.23%) was attributed to congenital hypothyroidism, multiple etiologies accounted for 22.3% (97/435), and 35.63% (155/435) were of unknown etiology. Of the jaundiced infants, 19.54% (85/435) had G6PD deficiency, while only 10.23% (70/684) of non-jaundiced infants had G6PD deficiency; this difference was found to be statistically significant (P < 0.001). Furthermore, the hemoglobin levels in the jaundiced infants with G6PD deficiency (146.85 ± 24.88 g/L) were lower than those without G6PD deficiency (156.30 ± 22.07 g/L) (P = 0.001). 65 jaundiced infants with G6PD deficiency underwent G6PD mutation testing, and six different genotypes were identified, including c.95A > G, c.392G > T, c.1024C > T, c.1311C > T, c.1376G > T, c.1388G > A, c.871G > A/c.1311C > T, c.392G > T/c.1388G > A, and c.1376G > T/c.1311C > T.65iciency. Conclusion: In newborns in Yangjiang, G6PD deficiency, infection, and neonatal hemolytic disease were identified as the main causes of hyperbilirubinemia and acute bilirubin encephalopathy. Specifically, Hemolytic factors in infants with G6PD deficiency may lead to reduced hemoglobin and increased bilirubin levels in jaundiced infants.

Covid-19 omicron variant infection in neonates of Guangdong province-a report of 52 cases.

Objective: To analyze the clinical characteristics of neonatal infection during the outbreak of COVID-19 omicron variant in Guangdong province of China. Method: The clinical data of neonates infected with COVID-19 omicron variant were collected from three hospitals of Guangdong province, their epidemiological history, clinical manifestation and prognosis were summarized. Results: From December 12, 2022 to January 15, 2023, a total of 52 neonates with COVID-19 infection were identified across three hospitals in Guangdong Province, including 34 males and 18 females. The age of diagnosis was 18.42 ± 6.32 days. 24 cases had clear contact history with adults who were suspected to be infected with COVID-19. The most common clinical manifestation was fever (43/52, 82.7%), the duration of fever was 1-8 days. The other clinical manifestations were cough (27/52, 51.9%), rales (21/52, 40.4%), nasal congestion (10/52, 19.2%), shortness of breath (2/52, 3.8%), and vomiting (4/52, 7.7%). C-reactive protein was only increased in 3 cases. Chest radiological examination was performed in 42 neonates, twenty-three cases showed abnormal chest radiographic findings, including ground-glass opacity and consolidation. Fifty cases were admitted with COVID-19 presentation, two cases were admitted for jaundice. The hospital stay was 6.59 ± 2.77 days. The clinical classification included 3 cases of severe COVID-19 and one critical case. Fifty-one cases were cured and discharged after general treatment, and one critical case with respiratory failure was intubated and transferred to another hospital. Conclusion: The COVID-19 omicron variant infection in neonates is usually mild. The clinical manifestation and laboratory results are not specific, and the short-term prognosis is good.

A retrospective analysis of preemptive pharmacogenomic testing in 22,918 individuals from China.

BACKGROUND: Pharmacogenomics (PGx) examines the influence of genetic variation on drug responses. With more and more Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines published, PGx is gradually shifting from the reactive testing of single gene toward the preemptive testing of multiple genes. But the profile of PGx genes, especially for the intra-country diversity, is not well understood in China. METHODS: We retrospectively collected preemptive PGx testing data of 22,918 participants from 20 provinces of China, analyzed frequencies of alleles, genotypes and phenotypes of pharmacogenes, predicted drug responses for each participant, and performed comparisons between different provinces. RESULTS AND CONCLUSION: After analyzing 15 pharmacogenes from CPIC guidelines of 31 drugs, we found that 99.97% of individuals may have an atypical response to at least one drug; the participants carry actionable genotypes leading to atypical dosage recommendation for a median of eight drugs. Over 99% of the participants were recommended a decreased warfarin dose based on genetic factors. There were 20 drugs with high-risk ratios from 0.18% to 58.25%, in which clopidogrel showed the highest high-risk ratio. In addition, the high-risk ratio of rasburicase in GUANGDONG (risk ratio (RR) = 13.17, 95%CI:4.06-33.22, p < 0.001) and GUANGXI (RR = 23.44, 95%CI:8.83-52.85, p < 0.001) were significantly higher than that in all provinces. Furthermore, the diversity we observed among 20 provinces suggests that preemptive PGx testing in different geographical regions in China may need to pay more attention to specific genes. These results emphasize the importance of preemptive PGx testing and provide essential evidence for promoting clinical implementation in China.

The gene spectrum of thalassemia in Yangjiang of western Guangdong Province.

Background: Thalassemia presents a higher incidence in southern China. The objective of this study is to analyze the genotype distribution of thalassemia in Yangjiang, a western city of Guangdong Province in China. Methods: The genotypes of suspected cases with thalassemia were tested by PCR and reverse dot blot (RDB). Unidentified rare thalassemia genotypes of the samples were further ascertained by PCR and direct DNA sequencing. Results: Among 22467 suspected cases with thalassemia, 7658 cases were found with thalassemia genotypes using our PCR-RDB kit. Among these 7658 cases, 5313 cases were found with α-thalassemia (α-thal) alone, --SEA/αα was the most common genotype, accounting for 61.75% of α-thal genotypes, and the following mutations were found: α3.7/αα, -α4.2/αα, αCSα/αα, αWSα/αα, and αQSα/αα. A total of 2032 cases were found with ß-thalassemia (ß-thal) alone. ßCD41-42/ßN, ßIVS-II-654/ßN, and ß-28/ßN accounted for 80.9% of all ß-thal genotypes, and the following genotypes were found: ßCD17/ßN, ßCD71-72/ßN, and ßE/ßN. Compound heterozygotes of ß-thal and ß-thalassemia homozygotes were identified in 11 and five cases, respectively, in this study. α-thal combined with ß-thal was identified in 313 cases, showing 57 genotype combinations of the coincidence of both Hb disorders; one extreme patient had a genotype of --SEA/αWSα and ßCD41-42/ß-28. In addition, four rare α-mutations (--THAI, HKαα, Hb Q-Thailand, and CD31 AGG>AAG) and six rare ß-mutations (CD39 CAG>TAG, IVS-Ⅱ-2 (-T), -90(C>T), Chinese Gγ+(Aγδß)0, CD104 (-G), and CD19 A>G) were also found in this study population. Conclusion: This study provided detailed genotypes of thalassemia in Yangjiang of western Guangdong Province in China and reflected the complexity of genotypes in this high-prevalence region, and this would be valuable for diagnosis and counseling for thalassemia in this area.

Realization of exceptional points along a synthetic orbital angular momentum dimension.

Exceptional points (EPs), at which more than one eigenvalue and eigenvector coalesce, are unique spectral features of non-Hermiticity (NH) systems. They exist widely in open systems with complex energy spectra. We experimentally demonstrate the appearance of paired EPs in a periodical-driven degenerate optical cavity along the synthetic orbital angular momentum dimension with a tunable parameter. The complex-energy band structures and the key features of EPs, i.e., their bulk Fermi arcs, parity-time symmetry breaking transition, energy swapping, and half-integer band windings, are directly observed by detecting the wavefront angle-resolved transmission spectrum. Our results demonstrate the flexibility of using the photonic synthetic dimensions to implement NH systems beyond their geometric dimension and EP-based sensing.

Molecular epidemiological investigation of G6PD deficiency in Yangjiang region, western Guangdong province.

Objectives: The prevalence of G6PD deficiency has not been reported in Yangjiang, a western city in Guangdong province. This study aims to investigate the molecular characteristics of G6PD deficiency in this region. Methods: Blood samples were collected from adults at a local hospital to screen for G6PD deficiency. The deficient samples were subjected to further analysis using PCR and reverse dot blot to determine the specific G6PD variants. Results: Among the 3314 male subjects, 250 cases of G6PD deficiency were found using the G6PD enzyme quantitative assay, resulting in a prevalence of 7.54% (250/3314) in the Yangjiang region. The prevalence of G6PD deficiency in females was 3.42% (176/5145). Out of the 268 cases of G6PD deficiency tested for G6PD mutations, reverse dot blot identified 20 different G6PD variants. The most common G6PD variant was c.1388G>A (81/268), followed by c.1376G>T (48/268), c.95A>G (32/268), c.1024C>T (9/268), c.392G>T (7/268), and c.871G>A/c.1311C>T (6/268). It was observed that c.871G>A was always linked to the polymorphism of c.1311C>T in this population. Conclusion: This investigation into G6PD deficiency in this area is expected to significantly improve our understanding of the prevalence and molecular characterization of this condition.

Topological band structure via twisted photons in a degenerate cavity.

Synthetic dimensions based on particles' internal degrees of freedom, such as frequency, spatial modes and arrival time, have attracted significant attention. They offer ideal large-scale lattices to simulate nontrivial topological phenomena. Exploring more synthetic dimensions is one of the paths toward higher dimensional physics. In this work, we design and experimentally control the coupling among synthetic dimensions consisting of the intrinsic photonic orbital angular momentum and spin angular momentum degrees of freedom in a degenerate optical resonant cavity, which generates a periodically driven spin-orbital coupling system. We directly characterize the system's properties, including the density of states, energy band structures and topological windings, through the transmission intensity measurements. Our work demonstrates a mechanism for exploring the spatial modes of twisted photons as the synthetic dimension, which paves the way to design rich topological physics in a highly compact platform.

Role of fibrosarcoma-induced CD11b+ myeloid cells and tumor necrosis factor-α in B cell responses.

The role of B cells in the anti-tumor immune response remains controversial. An increase in the number of B cells in the peripheral blood of some tumor patients has been associated with poor immunotherapy efficacy. However, the mechanism leading to the generation of these cells is not well-described. Using a fibrosarcoma model, we show that intraperitoneal administration of a xenogeneic antigen in tumor-bearing mice evokes large increases in antigen-specific serum immunoglobulin formation compared to tumor-naïve mice. An inability of tumor-bearing mice to induce enhanced antibody production after myeloid cell depletion suggests the antibody responses are CD11b+ myeloid cell-dependent. In vitro, CD11b+ myeloid cells promoted B cell proliferation, activation, and survival. High levels of tumor necrosis factor (TNF)-α were produced by CD11b+ cells, and TNF-α blockade inhibited B cell responses. CD11b+ cells appear to be important promoters of B cell responses and targeting B cells may increase the efficacy of immunotherapy in tumor-bearing hosts.

A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer.

BACKGROUND: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3-4 toxicity. METHODS: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. RESULTS: Reported grade ≤ 2 and 3-4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70-10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19-1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. CONCLUSION: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.

Allele frequency deviation (AFD) as a new prognostic model to predict overall survival in lung adenocarcinoma (LUAD).

BACKGROUND: Lung adenocarcinoma (LUAD) remains one of the world's most known aggressive malignancies with a high mortality rate. Molecular biological analysis and bioinformatics are of great importance as they have recently occupied a large area in the studies related to the identification of various biomarkers to predict survival for LUAD patients. In our study, we attempted to identify a new prognostic model by developing a new algorithm to calculate the allele frequency deviation (AFD), which in turn may assist in the early diagnosis and prediction of clinical outcomes in LUAD. METHOD: First, a new algorithm was developed to calculate AFD using the whole-exome sequencing (WES) dataset. Then, AFD was measured for 102 patients, and the predictive power of AFD was assessed using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and area under the curve (AUC). Finally, multivariable cox regression analyses were conducted to evaluate the independence of AFD as an independent prognostic tool. RESULT: The Kaplan-Meier analysis showed that AFD effectively segregated patients with LUAD into high-AFD-value and low-AFD-value risk groups (hazard ratio HR = 1.125, 95% confidence interval CI 1.001-1.26, p = 0.04) in the training group. Moreover, the overall survival (OS) of patients who belong to the high-AFD-value group was significantly shorter than that of patients who belong to the low-AFD-value group with 42.8% higher risk and 10% lower risk of death for both groups respectively (HR for death = 1.10; 95% CI 1.01-1.2, p = 0.03) in the training group. Similar results were obtained in the validation group (HR = 4.62, 95% CI 1.22-17.4, p = 0.02) with 41.6%, and 5.5% risk of death for patients who belong to the high and low-AFD-value groups respectively. Univariate and multivariable cox regression analyses demonstrated that AFD is an independent prognostic model for patients with LUAD. The AUC for 5-year survival were 0.712 and 0.86 in the training and validation groups, respectively. CONCLUSION: AFD was identified as a new independent prognostic model that could provide a prognostic tool for physicians and contribute to treatment decisions.

A seven-gene prognostic signature predicts overall survival of patients with lung adenocarcinoma (LUAD).

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common types in the world with a high mortality rate. Despite advances in treatment strategies, the overall survival (OS) remains short. Our study aims to establish a reliable prognostic signature closely related to the survival of LUAD patients that can better predict prognosis and possibly help with individual monitoring of LUAD patients. METHODS: Raw RNA-sequencing data were obtained from Fudan University and used as a training group. Differentially expressed genes (DEGs) for the training group were screened. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate cox regression analysis were conducted to identify the candidate prognostic genes and construct the risk score model. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic power and performance of the signature. Moreover, The Cancer Genome Atlas (TCGA-LUAD) dataset was further used to validate the predictive ability of prognostic signature. RESULTS: A prognostic signature consisting of seven prognostic-related genes was constructed using the training group. The 7-gene prognostic signature significantly grouped patients in high and low-risk groups in terms of overall survival in the training cohort [hazard ratio, HR = 8.94, 95% confidence interval (95% CI)] [2.041-39.2]; P = 0.0004), and in the validation cohort (HR = 2.41, 95% CI [1.779-3.276]; P < 0.0001). Cox regression analysis (univariate and multivariate) demonstrated that the seven-gene signature is an independent prognostic biomarker for predicting the survival of LUAD patients. ROC curves revealed that the 7-gene prognostic signature achieved a good performance in training and validation groups (AUC = 0.91, AUC = 0.7 respectively) in predicting OS for LUAD patients. Furthermore, the stratified analysis of the signature showed another classification to predict the prognosis. CONCLUSION: Our study suggested a new and reliable prognostic signature that has a significant implication in predicting overall survival for LUAD patients and may help with early diagnosis and making effective clinical decisions regarding potential individual treatment.

Nitrogen vacancy induced in situ g-C3N4 p-n homojunction for boosting visible light-driven hydrogen evolution.

Graphitic carbon nitride (g-C3N4) as a novel photocatalyst with great potentials has been extensively employed in solar-driven energy conversion. Herein, the novel in situ g-C3N4 p-n homojunction photocatalyst with nitrogen vacancies (NV-g-C3N4) is successfully fabricated via hydrothermal synthesis followed by two-step calcination. The in situ NV-g-C3N4 homojunction can be employed as an effective photocatalyst for hydrogen generation through water splitting under visible light, and the optimum rate constant of 3259.1 µmol.g-1.h-1 is achieved, which is 8.7 times as high as that of pristine g-C3N4. Moreover, the markedly increased photocatalytic performance is ascribed to the enhanced light utilization, large specific surface area and unique nitrogen-vacated p-n homojunction structure, which provides more active sites and improves the separation of photo-excited electron-hole pairs. Besides, the underlying mechanism for efficient charge transportation and separation is also proposed. This work demonstrates that the remodeling of g-C3N4 p-n homojunction with nitrogen vacancies is a feasible way as highly efficient photocatalysts and might inspire some new strategies for energy and environmental applications.

Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells.

RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms. Here, we demonstrate that DROSHA interacts with ß-Catenin to transactivate STC1 in an RNA cleavage-independent manner, contributing to breast cancer stem-like cell (BCSC) properties. DROSHA mRNA stability is enhanced by N6-methyladenosine (m6A) modification which is activated by AURKA in BCSCs. AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation. Moreover, binding of AURKA to DROSHA transcript further strengthens the binding of the m6A reader IGF2BP2 to stabilize m6A-modified DROSHA. In addition, wild-type DROSHA, but not an m6A methylation-deficient mutant, enhances BCSC stemness maintenance, while inhibition of DROSHA m6A modification attenuates BCSC traits. Our study unveils the AURKA-induced oncogenic m6A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype.

Longitudinal whole-genome sequencing reveals the evolution of MPAL.

PURPOSE: Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia and its progressive genomic basis over time remains unclear. We aimed to investigate the longitudinal genomic evolution of MPAL from diagnosis to relapse. METHODS: We performed whole genome sequencing (WGS) on bone marrow (BM) samples obtained at the four stages of this disease in a male patient with Philadelphia chromosome positive (Ph+) MPAL, including primary, complete cytogenetic remission (CCR), complete molecular remission (CMR), and relapse stage during the 3 year follow-up period. RESULTS: 156 single-nucleotide variants (SNVs) and indels were detected, which exhibited distinctive evolutionary behaviors. Seventeen mutations disappeared quickly upon DCTER treatment and never came back. Seven mutations, although disappeared initially, reoccurred with the withdrawal of TKI treatment. Notably, ten mutations emerged in spite of the active DCTER chemotherapy. Moreover, copy number loss played critical roles in monitoring MPAL progression, displaying 7, 0, 0, and 383 losses at the stages of primary, CCR, CMR, and relapse respectively. CONCLUSION: This longitudinal genomic investigation of the Ph+ MPAL patient established one MPAL evolution model in which the primary tumor acquired additional variations leading to tumor relapse. Moreover, the event of copy number loss remained a valuable hallmark in the progression of MPAL.

The roles of circRFWD2 and circINO80 during NELL-1-induced osteogenesis.

Bone defects caused heavy social and economic burdens worldwide. Nel-like molecule, type 1 (NELL-1) could enhance the osteogenesis and the repairment of bone defects, while the specific mechanism remains to be elucidated. Circular RNAs (circRNAs) have been found to play critical roles in the tissue development and serve as biomarkers for various diseases. However, it remains unclear that the expression patterns of circRNAs and the roles of them played in recombinant NELL-1-induced osteogenesis of human adipose-derived stem cells (hASCs). In this study, we performed RNA-sequencing to investigate the expression profiles of circRNAs in recombinant NELL-1-induced osteogenic differentiation and identified two key circRNAs, namely circRFWD2 and circINO80. These two circRNAs were confirmed to be up-regulated during recombinant NELL-1-induced osteogenesis, and knockdown of them affected the positive effect of NELL-1 on osteogenesis. CircRFWD2 and circINO80 could interact with hsa-miR-6817-5p, which could inhibit the osteogenesis. Silencing hsa-miR-6817-5p could partially reverse the negative effect of si-circRFWD2 and si-circINO80 on the osteogenesis. Therefore, circRFWD2 and circINO80 could regulate the expression of hsa-miR-6817-5p and influence the recombinant NELL-1-induced osteogenic differentiation of hASCs. It opens a new window to better understanding the effects of NELL-1 on the osteogenic differentiation of hASCs and provides potential molecular targets and novel methods for bone regeneration efficiently and safely.

High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study.

Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.