Sulfa-Michael Addition on Dehydroalanine: A Versatile Reaction for Protein Modifications.

Chemical modification of proteins has been widely applied in diagnostic and therapeutic processes. Here, we report a novel bioconjugation between sulfinic acids and amino acid dehydroalanine (Dha) in the context of both small molecules and proteins. This conjugation enables the rapid formation of sulfone linkages in a chemoselective and disulfide-compatible manner under biocompatible conditions with Dha residues chemically installed in proteins and thus provides a robust tool that is simple and has exquisite site selectivity for protein functionalization in a wide range.

The Methodological Quality of Observational Studies Examining the Risk of Pregnancy Drug Use on Congenital Malformations Needs Substantial Improvement: A Cross-Sectional Survey.

BACKGROUND AND OBJECTIVE: An increasing number of observational studies have investigated the risk of using drugs during pregnancy on congenital malformations. However, the credibility of the causal relationships drawn from these studies remains uncertain. This study aims to evaluate the potential methodological issues in existing observational studies. METHODS: We used a stepwise approach to investigate this issue. First, we identified observational studies published in 2020 that examined the risk of congenital malformations associated with medication use during pregnancy. We assessed the methodological characteristics for establishing causality, including study design, confounding control, and sensitivity analysis, and compared them between "core clinical journals" and "general journals." For studies reporting an increased risk of congenital malformations in core clinical journals, we searched for subsequent studies addressing the same research question published between January 2021 and May 2023 to assess the consistency of the literature. RESULTS: A total of 40 eligible studies were published in 2020, primarily focused on the safety of vitamin B12 and folic acid (n = 4), antidepressants (n = 4), and others (n = 32). Our findings suggest that only two (5.00%) studies used causal models to guide the identification of confounding, and only eight (20.00%) studies assessed the potential dose-response relationship. In all, 15 (37.50%) studies used propensity score analysis strategy to achieve "mimic-randomization." In addition, 22 studies (55.00%) performed sensitivity analyses, while 10 (45.45%) showed inconsistency with the primary outcome. Furthermore, 5 studies reported positive outcomes, whereas only 1 out of 11 studies demonstrated a positive correlation between drug usage during pregnancy and major malformations in subsequent studies. CONCLUSION: A significant portion of the studies has failed to sufficiently consider the essential methodological characteristics required to improve the credibility of causal inferences. The increased risk of congenital malformations documented in core clinical journal was not adequately replicated in subsequent studies.

The suboptimal clinical applicability of prognostic prediction models for severe postpartum hemorrhage: a meta-epidemiological study.

OBJECTIVES: To systematically investigate clinical applicability of the current prognostic prediction models for severe postpartum hemorrhage (SPPH). STUDY DESIGN AND SETTING: A meta-epidemiological study of prognostic prediction models was conducted for SPPH. A pre-designed structured questionnaire was adopted to extract the study characteristics, predictors and the outcome, modeling methods, predictive performance, the classification ability for high-risk individuals, and clinical use scenarios. The risk of bias among studies was assessed by the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: Twenty-two studies containing 27 prediction models were included. The number of predictors in the final models varied from 3 to 53. However, one-third of the models (11) did not clearly specify the timing of predictor measurement. Calibration was found to be lacking in 10 (37.0%) models. Among the 20 models with an incidence rate of predicted outcomes below 15.0%, none of the models estimated the area under the precision-recall curve, and all reported positive predictive values were below 40.0%. Only two (7.4%) models specified the target clinical setting, while seven (25.9%) models clarified the intended timing of model use. Lastly, all 22 studies were deemed to be at high risk of bias. CONCLUSION: Current SPPH prediction models have limited clinical applicability due to methodological flaws, including unclear predictor measurement, inadequate calibration assessment, and insufficient evaluation of classification ability. Additionally, there is a lack of clarity regarding the timing for model use, target users, and clinical settings. These limitations raise concerns about the reliability and usefulness of these models in real-world clinical practice.

Association between high-altitude polycythemia and hypertension: a cross-sectional study in adults at Tibetan ultrahigh altitudes.

The study aimed to evaluate the association between high-altitude polycythemia and hypertension in adults residing on Anduo County's plateau, which is located 4700 meters above sea level. A total of 387 individuals participated in the cross-sectional survey conducted between April and May of 2021. Interviews, physical inspections, and laboratory tests were employed to gather information about all of the subjects. The association between high-altitude polycythemia and hypertension was assessed using multivariable logistic regression models. The average age of the 387 participants was 32.6 ± 6.3 years. Of these participants, 260 (67%) were male. The overall prevalence of hypertension was 27.1% (57/380). When stratified by gender, the prevalence was 12.6% (16/127) in females and 34.2% (89/260) in males. The overall prevalence of high-altitude polycythemia was 19.6% (76/387). When stratified by gender, the prevalence was 26.2% (68/260) in males and 6.3% (8/127) in females. During logistic regression analysis, we found that participants with elevated hemoglobin per 10 g/L had a 26% greater risk of hypertension (adjusting for odds ratio [OR], 1.26; 95% confidence interval [CI], 1.11-1.44). Additionally, high-altitude polycythemia greatly increased the risk of hypertension in comparison to non-high-altitude polycythemia (OR, 3.01; 95% CI, 1.66-5.44, P < 0.001). The consistency of the results was further demonstrated by stratified and interaction analyses, showing that Hans individuals had a higher risk of hypertension. High-altitude polycythemia is positively associated with hypertension in adults residing at Tibetan ultrahigh altitudes. The results of the investigation may aid in the planning of future research and guide the development of targeted healthcare practices for high-altitude populations, particularly among Han Chinese residents of the Tibetan Plateau.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Dual-Functional AIE Fluorescent Probe for Visualization of Lipid Droplets and Photodynamic Therapy of Cancer.

Abnormal lipid droplets (LDs) are known to be intimately bound with the occurrence and development of cancer, allowing LDs to be critical biomarkers for cancers. Aggregation-induced emission luminogens (AIEgens), with efficient reactive oxygen species (ROS) production performance, are prime photosensitizers (PSs) for photodynamic therapy (PDT) with imaging. Therefore, the development of dual-functional fluorescent probes with aggregation-induced emission (AIE) characteristics that enable both simultaneous LD monitoring and imaging-guided PDT is essential for concurrent cancer diagnosis and treatment. Herein, we reported the development of a novel LD-targeting fluorescent probe (TDTI) with AIE performance, which was expected to realize the integration of cancer diagnosis through LD visualization and cancer treatment via PDT. We demonstrated that TDTI, with typical AIE characteristics and excellent photostability, could target LDs with high specificity, which enables the dynamic tracking of LDs in living cells, specific imaging of LDs in zebrafish, and the differentiation of cancer cells from normal cells for cancer diagnosis. Meanwhile, TDTI exhibited fast ROS generation ability (achieving equilibrium within 60 s) under white light irradiation (10 mW/cm2). The cell apoptosis assay revealed that TDTI effectively induced growth inhibition and apoptosis of HeLa cells. Further, the results of PDT in vivo indicated that TDTI had a good antitumor effect on the tumor-bearing mice model. Collectively, these results highlight the potential utility of the dual-functional fluorescent probe TDTI in the integrated diagnosis and treatment of cancer.

Wearable sensor supports in-situ and continuous monitoring of plant health in precision agriculture era.

Plant health is intricately linked to crop quality, food security and agricultural productivity. Obtaining accurate plant health information is of paramount importance in the realm of precision agriculture. Wearable sensors offer an exceptional avenue for investigating plant health status and fundamental plant science, as they enable real-time and continuous in-situ monitoring of physiological biomarkers. However, a comprehensive overview that integrates and critically assesses wearable plant sensors across various facets, including their fundamental elements, classification, design, sensing mechanism, fabrication, characterization and application, remains elusive. In this study, we provide a meticulous description and systematic synthesis of recent research progress in wearable sensor properties, technology and their application in monitoring plant health information. This work endeavours to serve as a guiding resource for the utilization of wearable plant sensors, empowering the advancement of plant health within the precision agriculture paradigm.

Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research.

Cancer cells need a greater supply of glucose mainly due to their aerobic glycolysis, known as the Warburg effect. Glucose transport by glucose transporter 1 (GLUT1) is the rate-limiting step for glucose uptake, making it a potential cancer therapeutic target. However, GLUT1 is widely expressed and performs crucial functions in a variety of cells, and its indiscriminate inhibition will cause serious side effects. In this study, we designed and synthesized a photocaged GLUT1 inhibitor WZB117-PPG to suppress the growth of cancer cells in a spatiotemporally controllable manner. WZB117-PPG exhibited remarkable photolysis efficiency and substantial cytotoxicity toward cancer cells under visible light illumination with minimal side effects, ensuring its safety as a potential cancer therapy. Furthermore, our quantitative proteomics data delineated a comprehensive portrait of responses in cancer cells under glucose deprivation, underlining the mechanism of cell death via necrosis rather than apoptosis. We reason that our study provides a potentially reliable cancer treatment strategy and can be used as a spatiotemporally controllable trigger for studying nutrient deprivation-related stress responses.

Investigation of statistical methods used in prognostic prediction models for obstetric care: A 10 year-span cross-sectional study.

INTRODUCTION: Obstetric care is a highly active area in the development and application of prognostic prediction models. The development and validation of these models often require the utilization of advanced statistical techniques. However, failure to adhere to rigorous methodological standards could greatly undermine the reliability and trustworthiness of the resultant models. Consequently, the aim of our study was to examine the current statistical practices employed in obstetric care and offer recommendations to enhance the utilization of statistical methods in the development of prognostic prediction models. MATERIAL AND METHODS: We conducted a cross-sectional survey using a sample of studies developing or validating prognostic prediction models for obstetric care published in a 10-year span (2011-2020). A structured questionnaire was developed to investigate the statistical issues in five domains, including model derivation (predictor selection and algorithm development), model validation (internal and external), model performance, model presentation, and risk threshold setting. On the ground of survey results and existing guidelines, a list of recommendations for statistical methods in prognostic models was developed. RESULTS: A total of 112 eligible studies were included, with 107 reporting model development and five exclusively reporting external validation. During model development, 58.9% of the studies did not include any form of validation. Of these, 46.4% used stepwise regression in a crude manner for predictor selection, while two-thirds made decisions on retaining or dropping candidate predictors solely based on p-values. Additionally, 26.2% transformed continuous predictors into categorical variables, and 80.4% did not consider nonlinear relationships between predictors and outcomes. Surprisingly, 94.4% of the studies did not examine the correlation between predictors. Moreover, 47.1% of the studies did not compare population characteristics between the development and external validation datasets, and only one-fifth evaluated both discrimination and calibration. Furthermore, 53.6% of the studies did not clearly present the model, and less than half established a risk threshold to define risk categories. In light of these findings, 10 recommendations were formulated to promote the appropriate use of statistical methods. CONCLUSIONS: The use of statistical methods is not yet optimal. Ten recommendations were offered to assist the statistical methods of prognostic prediction models in obstetric care.

Correlation analysis of clinical, pathological, imaging and genetic features of ground-glass nodule featured lung adenocarcinomas between high-risk and non-high-risk individuals.

BACKGROUND: Early stage lung adenocarcinomas manifested as ground-glass nodules (GGNs) are increasingly being detected, but screening and diagnosis for GGN-featured lung adenocarcinomas in different risk populations reach no agreement. OBJECTIVES: To analyze the clinical, pathological, imaging and genetic features of GGN-featured lung adenocarcinomas on high-resolution computed tomography (HRCT) in different risk groups. METHODS: Include patients with GGNs on HRCT surgically diagnosed as lung adenocarcinoma in the West China Hospital, Sichuan University from 2009 to 2021, and their clinical, pathological, imaging and gene sequencing data. RESULTS: According to Chinese Expert Consensus on Screening and Management of Lung Cancer, 1,800 patients with GGN-featured lung adenocarcinoma, 545 males (incl. 269 smokers) and 1,255 females (incl. 16 smokers), were divided into high-risk (509) and non-high-risk (1,291) groups. Among them, 1,095 were detected via physical examination. The mean age at diagnosis was 54.78 (23-84) and the mean time from detection to diagnosis was 9.59 months. There were more males than females in the high-risk group [288 (56.58%) vs 221 (43.42%)], just the opposite in the non-high-risk group [1,034 (80.09%) vs 257 (19.91%)] (both P < 0.001). No statistical difference was found in GGN detection way (P > 0.05). The frequency of invasive adenocarcinoma was higher in the high-risk group, while those of precursor lesions and minimally invasive adenocarcinoma were higher in the non-high-risk group (all P < 0.001). The preoperative follow-up time in the non-high-risk group was shorter (P < 0.05). A total of 711 gene mutations were observed in 473 patients with a ratio of non-high-risk to high-risk of 494:217. The incidence of EGFR mutation was not statistically significant (P = 0.824), while those of TP53 and KRAS mutations were higher in the high-risk group (P < 0.05). CONCLUSIONS: GGN-featured lung adenocarcinoma is dominated by non-high-risk female patients. Shorter preoperative follow-up in the non-high-risk group and no statistical difference in GGN detection way suggests the existing screening criteria for high-risk population may not suit GGN-featured lung cancer. In addition, the incidences of KRAS and TP53 mutations are higher in the high-risk group.

Effect of a mental health education intervention on children's life satisfaction and self-confidence in rural China.

Children living in rural areas may potentially experience low levels of life satisfaction and face challenges in developing self-confidence. The purpose of the current study was to examine the impact of a mental health education intervention on the life satisfaction and self-confidence of children residing in rural areas of China. A total of 1,001 children from grades 4 to 6 were randomly assigned to an intervention group (475 children, 250 boys, M = 11.57 years, SD = 1.082 years) and a control group (526 children, 279 boys, M = 11.38 years, SD = 0.980 years). Over 16 weeks, the intervention group received a mental health education program, while the control group did not. The levels of life satisfaction (including five dimensions: family, school, environmental, friends, and self-satisfaction) and self-confidence (including three dimensions: self-efficacy, self-assurance, and self-competence) were rated by all children at baseline and post-intervention. Results from paired samples t-test showed that post-intervention, the intervention group exhibited significant improvements in the areas of family, environmental, school, and self-satisfaction as well as self-efficacy, self-assurance, and self-competence. However, there was no significant improvement in friend satisfaction. Conversely, the control group showed decreases in school, environmental, and friend satisfaction, along with decreases in self-efficacy, self-assurance, and self-competence. No significant change was observed in family and self-satisfaction in this group. These findings emphasize the importance of implementing mental health education interventions for rural children, who are at risk for low life satisfaction and self-confidence. Some specific recommendations are provided for policymakers and practitioners.

Impact of maternal hepatitis B carrier status on congenital abnormalities: a systematic review and meta-analysis.

OBJECTIVES: This study aims to explore whether maternal hepatitis B carrier status is associated with an increased risk of congenital abnormalities. DESIGN: A systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, Embase (Ovid), Scopus, the China National Knowledge Infrastructure (CNKI) and the Wanfang databases. STUDY SELECTION: Five databases were searched systematically from inception to 7 September 2021. Cohort and case-control studies that investigated the association between maternal hepatitis B virus (HBV) infection and congenital abnormalities were included. This study was conducted according to MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently collected data, as well as assessed risk of bias by using Newcastle-Ottawa Scale. We pooled crude relative risk (cRR) and adjusted OR (aOR) by DerSimonian-Laird random-effects model. Heterogeneity was explored by I 2 statistics, Cochran's Q test. Several subgroup analyses and sensitivity analyses were performed. RESULTS: In total, 14 studies involving 16 205 pregnant women exposed to HBV were included. The pooled cRR of 1.15 (95% CI: 0.92 to 1.45; 14 studies included) showed a marginal but not significant association between maternal HBV-carrier status and congenital abnormalities. However, the pooled aOR of 1.40 (95% CI: 1.01 to 1.93; 8 studies included) indicated that pregnant women with HBV infection might be associated with a higher risk of congenital abnormalities. Subgroup analyses of adjusted data showed a higher pooling cRR or aOR on high prevalence HBV infection populations, as well as studies from Asia and Oceania. CONCLUSIONS: Maternal hepatitis B carrier status might be at potential risk for congenital abnormalities. The existing evidence was not sufficient to draw a firm conclusion. Additional studies may be warranted to confirm the association. PROSPERO REGISTRATION NUMBER: CRD42020205459.

The use of Chinese herbal medicines throughout the pregnancy life course and their safety profiles: a population-based cohort study.

BACKGROUND: Chinese herbal medicines have been long used among pregnant populations in China. However, despite the high susceptibility of this population to drug exposure, it continued to remain unclear about how often they were used, to what extent they were used at different pregnancy stages, and whether their use was based on sound safety profiles, particularly when used in combination with pharmaceutical drugs. OBJECTIVE: This descriptive cohort study aimed to systematically investigate the use of Chinese herbal medicines throughout pregnancy and their safety profiles. STUDY DESIGN: A large medication use cohort was developed by linking a population-based pregnancy registry and a population-based pharmacy database, which documented all prescriptions at both outpatients and inpatients from conception to 7 days after delivery, including pharmaceutical drugs and processed Chinese herbal medicine formulas that were approved by the regulatory authority and prepared under the guidance of national quality standards. The prevalence of the use of Chinese herbal medicine formulas, prescription pattern, and combination use of pharmaceutical drugs throughout pregnancy were investigated. Multivariable log-binomial regression was performed to assess temporal trends and further explore the potential characteristics associated with the use of Chinese herbal medicines. Of note, 2 authors independently conducted a qualitative systematic review of patient package inserts of the top 100 Chinese herbal medicine formulas used to identify their safety profiles. RESULTS: This study included 199,710 pregnancies; of those pregnancies, 131,235 (65.71%) used Chinese herbal medicine formulas, including 26.13% during pregnancy (corresponding to 14.00%, 8.91%, and 8.26% in the first, second, and third trimesters of pregnancy) and 55.63% after delivery. The peak uses of Chinese herbal medicines occurred between 5 and 10 weeks of gestation. The use of Chinese herbal medicines significantly increased over the years (from 63.28% in 2014 to 69.59% in 2018; adjusted relative risk, 1.11; 95% confidence interval, 1.10-1.13), which was particularly great during pregnancy (from 18.47% in 2014 to 32.46% in 2018; adjusted relative risk, 1.84; 95% confidence interval, 1.77-1.90). Our study observed 291,836 prescriptions involving 469 Chinese herbal medicine formulas, and the top 100 most used Chinese herbal medicines accounted for 98.28% of the total prescriptions. Of those, a third (33.39%) were dispensed at outpatient visits; 6.79% were external use, and 0.29% were administered intravenously. However, Chinese herbal medicines were very often prescribed in combination with pharmaceutical drugs (94.96% overall), involving 1175 pharmaceutical drugs with 1,667,459 prescriptions. The median of pharmaceutical drugs prescribed in combination with Chinese herbal medicines per pregnancy was 10 (interquartile range, 5-18). The systematic review of drug patient package inserts found that the 100 most frequently prescribed Chinese herbal medicines contained a total of 240 herb constituents (median, 4.5); 7.00% were explicitly indicated for pregnancy or postpartum conditions; 43.00% were reported with efficacy or safety data from randomized controlled trials. Information was lacking about whether the medications had any reproductive toxicity, were excreted in human milk, or crossed the placenta. CONCLUSION: The use of Chinese herbal medicines was prevalent throughout pregnancy and increased over the years. The use of Chinese herbal medicines peaked in the first trimester of pregnancy and was very often used in combination with pharmaceutical drugs. However, their safety profiles were mostly unclear or incomplete, suggesting a strong need for postapproval surveillance for the use of Chinese herbal medicines during pregnancy.

The dual detection of formaldehydes and sulfenic acids with a reactivity fluorescent probe in cells and in plants.

In order to reveal the inter-relationship between protein sulfenic acid (RSOH) and formaldehyde (FA) in different physiological processes, development of tools that are capable of respective and continuous detection for both species is highly valuable. Herein, we reported an "off-on" sensor NA-SF for dual detection of RSOH and FA in cells and plant tissues. Importantly, the highly desirable attribute of the probe NA-SF combined with TCEP, makes it possible to monitor endogenous both RSOH and FA in living cells and plants tissues. NA-SF has been applied successfully in detecting RSOH and FA at physiological concentrations in HeLa, HepG2, A549 cells. Furthermore, the application of NA-SF in evaluating the RSOH and FA level in Arabidopsis thaliana roots of different growth stages are performed. The results show that the level of RSOH and FA in Arabidopsis thaliana roots correlates well with their growth stages, which suggests that both RSOH and FA might play important roles in promoting plant growth and roots elongation. And it also implied a potential application for the biological and pathological research of RSOH and FA, especially in plant physiology. Therefore, we expect NA-SF could provide a convenient and robust tool for better understanding the physiological and pathological roles of RSOH and FA.

The reporting of prognostic prediction models for obstetric care was poor: a cross-sectional survey of 10-year publications.

BACKGROUND: To investigate the reporting of prognostic prediction model studies in obstetric care through a cross-sectional survey design. METHODS: PubMed was searched to identify prognostic prediction model studies in obstetric care published from January 2011 to December 2020. The quality of reporting was assessed by the TRIPOD checklist. The overall adherence by study and the adherence by item were calculated separately, and linear regression analysis was conducted to explore the association between overall adherence and prespecified study characteristics. RESULTS: A total of 121 studies were included, while no study completely adhered to the TRIPOD. The results showed that the overall adherence was poor (median 46.4%), and no significant improvement was observed after the release of the TRIPOD (43.9 to 46.7%). Studies including both model development and external validation had higher reporting quality versus those including model development only (68.1% vs. 44.8%). Among the 37 items required by the TRIPOD, 10 items were reported adequately with an adherence rate over of 80%, and the remaining 27 items had an adherence rate ranging from 2.5 to 79.3%. In addition, 11 items had a report rate lower than 25.0% and even covered key methodological aspects, including blinding assessment of predictors (2.5%), methods for model-building procedures (4.5%) and predictor handling (13.5%), how to use the model (13.5%), and presentation of model performance (14.4%). CONCLUSIONS: In a 10-year span, prognostic prediction studies in obstetric care continued to be poorly reported and did not improve even after the release of the TRIPOD checklist. Substantial efforts are warranted to improve the reporting of obstetric prognostic prediction models, particularly those that adhere to the TRIPOD checklist are highly desirable.

Mitochondrion-targeting and in situ photocontrolled protein delivery via photocages.

Defects in mitochondrial proteostasis contribute to many disorders, including cancer, neurodegeneration, and metabolic and genetic diseases. A strategy aimed at restoring the damaged mitochondrial proteostasis is the mitochondrion-targeting and carrier-free delivery of exogenous functional proteins that can replace the endogenous dysfunctional proteins. The modification of a protein with a photolabile protecting group (PPG, i.e., photocage group) can be activated in situ by response to illumination, leading to release of the protein from its photocage. Here, the Cys and peptide photocages with coumarin were first prepared and characterized for proof of concept. Then, we designed a pair of photocage groups PPG-RhB and PPG-TPP using coumarin and mitochondrion-targeting Rhodamine B (RhB) and triphenylphosphine (TPP), and another pair of organelle-nontarget photocage groups Br-PPG and NO2-PPG for comparison. The proteins modified with these two pairs of photocage groups undergo photolysis in solutions, and can penetrate cell membrane toward their destinations in the carrier-free fashions. The intracellular protein photocages are in situ activated by illumination at 405 nm, and the proteins are released from their photocages in mitochondria and cytoplasm, respectively. This strategy of light-responsive and carrier-free cellular delivery enables mitochondrial and cytoplasmic accumulation of exogenous proteins.

SAXS Examinations of the Redox-Dependent Formation of a DNA-SOD1 Complex.

Cu/Zn superoxide dismutase (SOD1) plays a key role in the maintenance of cellular reactive oxygen species (ROS) homeostasis as an antioxidant enzyme. We recently found that SOD1 is involved in the regulation of gene expression in response to changes in cellular ROS levels by binding to DNA-specific sequences. Moreover, the SOD1 binding to DNA was observed to be redox-dependent in solutions. Thus, we examined the redox-dependent DNA binding of SOD1 by multiple measurements, including small-angle X-ray scattering (SAXS), indicating the redox-dependent formation of a DNA-SOD1 complex in solutions. The redox-dependent formation of the DNA-SOD1 complex could underlie the SOD1 regulation of gene expression.

Catalytic Asymmetric Vinylogous and Bisvinylogous Propargylic Substitution.

Distinct regio- and enantioselectivity control in copper-catalyzed vinylogous and bisvinylogous propargylic substitution has been accomplished by using a novel chiral N,N,P ligand. The developed method provides an efficient and selective approach to an array of highly enantioenriched alkynyl unsaturated carbonyl compounds. Salient features include excellent functional group tolerance and broad substrate scope. The synthetic utility of the developed method is further demonstrated by a gram-scale synthesis and by application to a range of transformations including enantioselective synthesis of unique challenging compounds.

Clinical data from the real world: Efficacy analysis of ceritinib (450mg) in ALK-rearrangement non-small-cell lung cancer patients with brain metastases in China.

Objectives: The real-world intracranial efficacy data of ceritinib at a dose of 450 mg quaque die (QD) are currently unavailable. Therefore, we evaluated the intracranial efficacy of ceritinib (450 mg QD) in anaplastic lymphoma kinase (ALK)-rearrangement NSCLC patients in China. Materials and Methods: In total, 57 ALK-rearrangement NSCLC patients with brain metastases (BM) were enrolled retrospectively in this real-world study. Of these, 53 patients experienced progression at baseline during or after prior crizotinib administration, and 24 patients received prior brain radiotherapy. Patients received ceritinib (450 mg QD) treatment. Intracranial efficacy [objective response rate (ORR) and disease control rate (DCR)] was evaluated according to the Response Assessment in Neuro-Oncology (RANO) standard; progression-free survival (PFS) and adverse events (AEs) data were obtained through follow-ups. Results: The intracranial ORR and DCR of ceritinib were 73.7% and 93.0%, respectively. The median intracranial PFS in patients reaching the endpoint was 8.75 months, whereas the median intracranial PFS in all patients was not reached and predicted to be not evaluable (NE) (95% CI: 12.9-NE). The estimated 12-month event-free probability (EFP) of intracranial lesions was 68.1%. A subgroup analysis revealed that the estimated 12-month EFP of intracranial lesions was relatively higher in patients with prior brain radiotherapy (93.8% vs. 47.1%, P = 0.0006). Conclusion: Ceritinib administered at 450 mg QD to ALK-rearrangement NSCLC patients with BM in China exhibited superior ORR and DCR, as well as PFS and event free probability. The estimated 12-month EFP for intracranial lesions improved in patients with prior brain radiotherapy.

Dose-response association between maternal pre-pregnancy bodyweight and gestational diabetes mellitus following ART treatment: a population-based cohort study.

BACKGROUND: The impact of maternal pre-pregnancy bodyweight on gestational diabetes mellitus (GDM) following assisted reproductive technology (ART) treatment has been insufficiently investigated. The aim of this study was to investigate the association between maternal pre-pregnancy bodyweight and GDM following ART. METHODS: From January 2014 to March 2019, this population-based retrospective cohort study included pregnancies achieved by ART treatment in a pregnancy registration database in China. Multivariate regression analysis and restricted cubic splines were used to explore the association between bodyweight and GDM. RESULTS: A total of 6,598 pregnancies were included. The incidence of GDM was 26.0% (1715/6598). A total of 868 (13.2%) pregnant women were underweight, 665 (10.8%) were overweight, and 145 (2.20%) were obesity. We found a linear dose-response relation between maternal body mass index and GDM by restricted cubic splines, where one unit body mass index increase was associated with the 15% elevated risk of GDM (adjusted odds ratio [OR] 1.15, 95% CI 1.08-1.22). Compared to the normal weight group, maternal underweight was associated with lower risk of GDM (adjusted OR 0.68, 95% CI 0.57-0.82), while increased risk was found for overweight (adjusted OR 1.54 95% CI 1.29-1.84) and obesity (adjusted OR 1.74, 95% CI 1.23-2.47). CONCLUSIONS: Our study found a linear dose-effect relationship between pre-pregnancy bodyweight and GDM following ART treatment. The findings in this study support the clinical recommendation of advising women with overweight or obesity to lose weight prior to ART treatment.