Novel Anthraquinone-Based Benzenesulfonamide Derivatives and Their Analogues as Potent Human Carbonic Anhydrase Inhibitors with Antitumor Activity: Synthesis, Biological Evaluation, and In Silico Analysis.

In this study, we designed two series of novel anthraquinone-based benzenesulfonamide derivatives and their analogues as potential carbonic anhydrase inhibitors (CAIs) and evaluated their inhibitory activities against off-target human carbonic anhydrase II (hCA II) isoform and tumor-associated human carbonic anhydrase IX (hCA IX) isoform. Most of these compounds exhibited good inhibitory activities against hCA II and IX. The compounds that exhibited the best hCA inhibition were further studied against the MDA-MB-231, MCF-7, and HepG2 cell lines under hypoxic and normoxic conditions. Additionally, the compounds exhibiting the best antitumor activity were subjected to apoptosis and mitochondrial membrane potential assays, which revealed a significant increase in the percentage of apoptotic cells and a notable decrease in cell viability. Molecular docking studies were performed to demonstrate the presence of numerous hydrogen bonds and hydrophobic interactions between the compounds and the active site of hCA. Absorption, distribution, metabolism, excretion (ADME) predictions showed that all of the compounds had good pharmacokinetic and physicochemical properties.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

High-speed and energy-efficient non-volatile silicon photonic memory based on heterogeneously integrated memresonator.

Recently, interest in programmable photonics integrated circuits has grown as a potential hardware framework for deep neural networks, quantum computing, and field programmable arrays (FPGAs). However, these circuits are constrained by the limited tuning speed and large power consumption of the phase shifters used. In this paper, we introduce the memresonator, a metal-oxide memristor heterogeneously integrated with a microring resonator, as a non-volatile silicon photonic phase shifter. These devices are capable of retention times of 12 hours, switching voltages lower than 5 V, and an endurance of 1000 switching cycles. Also, these memresonators have been switched using 300 ps long voltage pulses with a record low switching energy of 0.15 pJ. Furthermore, these memresonators are fabricated on a heterogeneous III-V-on-Si platform capable of integrating a rich family of active and passive optoelectronic devices directly on-chip to enable in-memory photonic computing and further advance the scalability of integrated photonic processors.

A 5 × 200 Gbps microring modulator silicon chip empowered by two-segment Z-shape junctions.

Optical interconnects have been recognized as the most promising solution to accelerate data transmission in the artificial intelligence era. Benefiting from their cost-effectiveness, compact dimensions, and wavelength multiplexing capability, silicon microring resonator modulators emerge as a compelling and scalable means for optical modulation. However, the inherent trade-off between bandwidth and modulation efficiency hinders the device performance. Here we demonstrate a dense wavelength division multiplexing microring modulator array on a silicon chip with a full data rate of 1 Tb/s. By harnessing the two individual p-n junctions with an optimized Z-shape doping profile, the inherent trade-off of silicon depletion-mode modulators is greatly mitigated, allowing for higher-speed modulation with energy consumption of sub-ten fJ/bit. This state-of-the-art demonstration shows that all-silicon modulators can practically enable future 200 Gb/s/lane optical interconnects.

Association of radiotherapy for stage I-III breast cancer survivors and second primary malignant cancers: a population-based study.

PURPOSE: With life span extending, breast cancer survivors may face the possibility of developing second primary cancers (SPCs). The objective of this research is to investigate the risk factors, risk attribute to radiotherapy and the survivalship for SPCs. METHODS: A total of 445 523 breast cancer patients were enrolled from Surveillance, Epidemiology, and End Results database in 2000-2018. The risk factors for SPCs development were confirmed by competing risk model, and then were integrated to the nomogram establishment. The cumulative incidence of SPCs including SBC (second breast cancer), SGC (second gynecological cancer), and SLC (second lung cancer) were estimated. The radiotherapy-associated risk for SPCs were evaluated by Poisson regression in radiotherapy and no-radiotherapy. Propensity score matching was used to reduce possible bias for survival comparison. RESULTS: There were 57.63% patients in radiotherapy. The risk factors for developing SPCs were age, year, race, tumor size, stage, radiotherapy, grade, surgery, and histology. The cumulative incidence of SPCs was 7.75% in no-radiotherapy and 10.33% in radiotherapy. SLC, SBC, and SGC also appeared the similar results. The increased risk of developing SPCs were associated with radiotherapy in majority subgroups. The dynamic radiotherapy-associated risk for SPCs by age slightly increased risk was observed. Regardless radiotherapy or no-radiotherapy, the 10-year overall survival for SBC (radiotherapy: 59.41%; no-radiotherapy: 55.53%) and SGC (radiotherapy: 48.61%; no-radiotherapy: 35.53%) were worse than that among matched patients with only primary cancers. CONCLUSIONS: Breast cancer survivors remained a high radiotherapy-associated risk for developing SPCs. The prognosis in radiotherapy was better than in no-radiotherapy for some specific SPCs. Largely attention should be paid to these patients.

Effect of activated carbon microstructure and adsorption mechanism on the efficient removal of chlorophyll a and chlorophyll b from Andrographis paniculata extract.

In order to reveal the effect of activated carbon (AC) properties on the adsorption of chlorophyll a (Chl a) and chlorophyll b (Chl b) in Andrographis paniculata extract, four commercial activated carbons were first tested and characterized. The results showed that activated carbon 1 (AC1) had the best surface area, pore structure and adsorption capacity. Therefore, adsorption isotherms, adsorption kinetics and adsorption mechanism were further carried out on AC1. The application of Langmuir model (R2 > 0.978) and Freundlich model (R2 > 0.977) indicated that the adsorption process of Chl a and Chl b on AC1 may be a complex adsorption process of single-layer and multilayer adsorption. The adsorption kinetics indicated that the pseudo-second-order kinetic model (R2 > 0.999) was dominant and was mainly chemisorption. The intra-particle diffusion model (R2 > 0.937) shows that the intra-particle diffusion is the rate-limiting step. The decrease of adsorption of AC1 to Chl a and Chl b due to the oxidation of acrylic acid proves the importance of π-π interaction.

Overlooked impact of less severe physical violence on antenatal care visits: Findings from South Asia.

Background: In South Asia, women often experience intimate partner violence (IPV) and have limited access to maternal health services (MHS). However, the effects of IPV on antenatal care (ANC) visits remain unclear. This study aimed to examine the impact of IPV of different forms and severities on ANC visits in South Asia. Methods: This cross-sectional study used the latest available data from demographic and health surveys conducted in Bangladesh, India, Afghanistan, Nepal, Maldives, and Pakistan. The study sampled 4467 women who had given birth within the past 12 months and were interviewed for IPV. IPV was measured by binary variables indicating the presence of physical violence (PV), categorised into less severe (LSPV) and severe physical violence (SPV), emotional violence (EV), and sexual violence (SV). ANC utilization was measured using binary variables indicating whether respondents had any, at least four, or at least eight ANC visits, as recommended by World Health Organization (WHO). Logistic regressions adjusted for survey weights were used to assess associations between ANC utilization and exposure to IPV during pregnancy and lifetime. Results: The prevalence of LSPV, SPV, EV, and SV during pregnancy were 14.5%, 4.4%, 11.6%, and 4.1%. LSPV experience during pregnancy was associated with decreased likelihoods of at least four ANC visits (odds ratio (OR) = 0.55; 95% confidence interval (CI) = 0.40-0.76) and eight ANC visits (OR = 0.53; 95% CI = 0.31-0.90). Results of lifetime exposure to IPV followed similar patterns. Lifetime exposure to LSPV was associated with decreased likelihoods of at least four ANC visits (OR = 0.55; 95% CI = 0.41-0.74) and eight ANC visits (OR = 0.47; 95% CI = 0.29-0.77). Conclusion: This study highlights the negativities of LSPV on the frequency of women seeking ANC visits. Policies are necessary to identify women at risk of the often-overlooked LSPV early and provide protective interventions to promote maternal health in South Asia.

Relationship between diabetic knowledge, attitudes and practices among patients with diabetes in China: a structural equation model.

OBJECTIVES: Whether the routine delivery of diabetes-related knowledge can change patients' attitudes and hence influence their self-management activities remains unknown in primary healthcare settings in China. Thus, this study aims to explore the complex transformation process between knowledge, attitude and practice (KAP) among patients with diabetes in a city in China. DESIGN: A cross-sectional study. SETTING: Yuhuan City, Zhejiang Province, China. PARTICIPANTS: A total of 803 patients with diabetes were invited to attend a questionnaire survey and 782 patients with type 2 diabetes completed the survey. The average age of participants was 58.47 years old, 48.21% of whom only attended primary school or below. PRIMARY AND SECONDARY OUTCOME MEASURES: A questionnaire based on existing scales and expert consultation was applied to assess patients' socio-demographic information (SI), disease progression risk and diabetes-related KAP. A structural equation model was built to analyse the relationships between patients' characteristics and KAP. RESULTS: No significant association was found between patients' knowledge and attitude (ß=0.01, p=0.43). Better knowledge and attitude were both found to be associated with better diet and physical activities (ß=0.58, p<0.001; ß=0.46, p=0.01). However, patients with a more positive attitude toward diabetic care showed worse foot care practice (ß=-0.13, p=0.02), while better knowledge was associated with better foot care practice (ß=0.29, p<0.001). In addition, patients with higher SI (ß=0.88, p<0.001) and/or disease progression risk (ß=0.42, p<0.001) tended to present higher levels of disease knowledge. CONCLUSIONS: While successful KAP transformation has been achieved in practice for diet and physical activities, there is a need to improve foot care practice. Health education should also prioritise the prevention, detection and care of diabetic foot. Also, appropriate methods should be adopted to deliver health education to vulnerable patients, such as the elderly, those living in rural areas, those with minimal education, the unemployed and low-income patients.

Developing and evaluating an interprofessional shared decision-making care model for patients with perinatal depression in maternal care in urban China: a study protocol.

BACKGROUND: The majority of patients with perinatal depression (PND) in China do not receive adequate treatment. As forming a therapeutic alliance with patients is crucial for depression treatment, shared decision-making (SDM) shows promise in promoting patients' uptake of evidence-based mental health services, but its impact on patient outcomes and implementation in real-world maternal care remain uncertain. Therefore, this study aims to develop and evaluate an interprofessional shared decision-making (IP-SDM) model for PND to enhance maternal mental health services. METHODS: This study contains four research phases: feasibility testing (Phase 1), toolkit development (Phase 2), usability evaluation (Phase 3), and effectiveness evaluation (Phase 4). During the development stage, focus group interviews will be conducted with expectant and new mothers, as well as maternal care providers for feasibility testing. A toolkit, including a patient decision aid along with its user guide and training materials, will be developed based on the findings of Phase 1 and syntheses of up-to-date evidence and appraised by the Delphi method. Additionally, a cognitive task analysis will be used for assessing the usability of the toolkit. During the evaluation stage, a prospective randomized controlled trial embedded in a mixed methods design will be used to evaluate the effectiveness and cost-effectiveness of the IP-SDM care model. The study targets to recruit 410 expectant and new mothers who screen positive for depression. They will be randomly assigned to either an intervention group or a control group in a 1:1 ratio. Participants in the intervention group will receive decision aid, decision coaching, and clinical consultation, in addition to usual services, while the control group will receive usual services. The primary outcome is the quality of decision-making process, and the secondary outcomes include SDM, mental health service utilization and costs, depressive symptoms, and health-related quality of life. In-depth interviews will be used to explore the facilitating and hindering factors of SDM. DISCUSSION: This study will develop an IP-SDM care model for PND that can be implemented in maternal care settings in China. This study will contribute to the understanding of how SDM impacts mental health outcomes and facilitate the integration of mental health services into maternal care. TRIAL REGISTRATION: ChiCTR2300072559. Registered on 16 June 2023.

Host genetic variation drives the differentiation in the ecological role of the native Miscanthus root-associated microbiome.

BACKGROUND: Microbiome recruitment is influenced by plant host, but how host plant impacts the assembly, functions, and interactions of perennial plant root microbiomes is poorly understood. Here we examined prokaryotic and fungal communities between rhizosphere soils and the root endophytic compartment in two native Miscanthus species (Miscanthus sinensis and Miscanthus floridulus) of Taiwan and further explored the roles of host plant on root-associated microbiomes. RESULTS: Our results suggest that host plant genetic variation, edaphic factors, and site had effects on the root endophytic and rhizosphere soil microbial community compositions in both Miscanthus sinensis and Miscanthus floridulus, with a greater effect of plant genetic variation observed for the root endophytic communities. Host plant genetic variation also exerted a stronger effect on core prokaryotic communities than on non-core prokaryotic communities in each microhabitat of two Miscanthus species. From rhizosphere soils to root endophytes, prokaryotic co-occurrence network stability increased, but fungal co-occurrence network stability decreased. Furthermore, we found root endophytic microbial communities in two Miscanthus species were more strongly driven by deterministic processes rather than stochastic processes. Root-enriched prokaryotic OTUs belong to Gammaproteobacteria, Alphaproteobacteria, Betaproteobacteria, Sphingobacteriia, and [Saprospirae] both in two Miscanthus species, while prokaryotic taxa enriched in the rhizosphere soil are widely distributed among different phyla. CONCLUSIONS: We provide empirical evidence that host genetic variation plays important roles in root-associated microbiome in Miscanthus. The results of this study have implications for future bioenergy crop management by providing baseline data to inform translational research to harness the plant microbiome to sustainably increase agriculture productivity. Video Abstract.

Topological analysis of functional connectivity in Parkinson's disease.

Parkinson's disease (PD) is a clinically heterogeneous disorder, which mainly affects patients' motor and non-motor function. Functional connectivity was preliminary explored and studied through resting state functional magnetic resonance imaging (rsfMRI). Through the topological analysis of 54 PD scans and 31 age-matched normal controls (NC) in the Neurocon dataset, leveraging on rsfMRI data, the brain functional connection and the Vietoris-Rips (VR) complex were constructed. The barcodes of the complex were calculated to reflect the changes of functional connectivity neural circuits (FCNC) in brain network. The 0-dimensional Betti number ß0 means the number of connected branches in VR complex. The average number of connected branches in PD group was greater than that in NC group when the threshold δ ≤ 0.7. Two-sample Mann-Whitney U test and false discovery rate (FDR) correction were used for statistical analysis to investigate the FCNC changes between PD and NC groups. In PD group, under threshold of 0.7, the number of FCNC involved was significantly differences and these brain regions include the Cuneus_R, Lingual_R, Fusiform_R and Heschl_R. There are also significant differences in brain regions in the Frontal_Inf_Orb_R and Pallidum_R, when the threshold increased to 0.8 and 0.9 (p < 0.05). In addition, when the length of FCNC was medium, there was a significant statistical difference between the PD group and the NC group in the Neurocon dataset and the Parkinson's Progression Markers Initiative (PPMI) dataset. Topological analysis based on rsfMRI data may provide comprehensive information about the changes of FCNC and may provide an alternative for clinical differential diagnosis.

Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

Epilepsy-associated genes: an update.

PURPOSE: To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence. METHODS: Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy. RESULTS: Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources. SIGNIFICANCE: Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.

Pharmacological Effects of Astragaloside IV: A Review.

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb's quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS-IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.

NEXMIF variants are associated with epilepsy with or without intellectual disability.

OBJECTIVES: Variants in NEXMIF had been reported associated with intellectual disability (ID) without epilepsy or developmental epileptic encephalopathy (DEE). It is unkown whether NEXMIF variants are associated with epilepsy without ID. This study aims to explore the phenotypic spectrum of NEXMIF and the genotype-phenotype correlations. MATERIALS AND METHODS: Trio-based whole-exome sequencing was performed in patients with epilepsy. Previously reported NEXMIF variants were systematically reviewed to analyze the genotype-phenotype correlations. RESULTS: Six variants were identified in seven unrelated cases with epilepsy, including two de novo null variants and four hemizygous missense variants. The two de novo variants were absent in all populations of gnomAD and four hemizygous missense variants were absent in male controls of gnomAD. The two patients with de novo null variants exhibited severe developmental epileptic encephalopathy. While, the patients with hemizygous missense variants had mild focal epilepsy with favorable outcome. Analysis of previously reported cases revealed that males with missense variants presented significantly higher percentage of normal intellectual development and later onset age of seizure than those with null variants, indicating a genotype-phenotype correlation. CONCLUSION: This study suggested that NEXMIF variants were potentially associated with pure epilepsy with or without intellectual disability. The spectrum of epileptic phenotypes ranged from the mild epilepsy to severe developmental epileptic encephalopathy, where the epileptic phenotypes variability are potentially associated with patients' gender and variant type.

LiCoO2 cathode surface modification with optimally structured Li3PO4 for outstanding high-voltage cycling performance.

While researchers often adopt a higher operating voltage to further enlarge the actual specific capacity of LCO to expand its application scope and market share, this triggers some more intractable issues in that the capacity decays obviously and causes the attendant problem of safety. Li3PO4 shows the advantage of increasing the energy density of lithium-ion batteries due to its characteristic ionic conduction when coated onto an LCO cathode. Enhancing the conductivity of cathode materials is the key factor in the success of raising their operating voltage to meet emerging market demands. Here, we report a direct facile coprecipitation method for coating crystalized Li3PO4 onto an LCO surface that enables balancing the ionic conductivity and chemical stability. LCO@ Li3PO4 crystalline lithium phosphate can generate superior electrical contact with the cathode material for high capacity and effectively stabilize the cathode surface by reducing the formation of SEI/CEI to prolong the cycle life. The optimized LP-3 cathode can deliver a high initial discharge capacity of 181 mA h g-1 at 0.5C, with a capacity retention of 75% after 200 cycles. This study introduces a competitive strategy to produce a high-voltage LCO cathode via the most viable and economical method.

d-lactate modulates M2 tumor-associated macrophages and remodels immunosuppressive tumor microenvironment for hepatocellular carcinoma.

The polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype demonstrates great potential for remodeling the immunosuppressive tumor microenvironment (TME) of hepatocellular carcinoma (HCC). d-lactate (DL; a gut microbiome metabolite) acts as an endogenous immunomodulatory agent that enhances Kupffer cells for clearance of pathogens. In this study, the potential of DL for transformation of M2 TAMs to M1 was confirmed, and the mechanisms underlying such polarization were mainly due to the modulation of phosphatidylinositol 3-kinase/protein kinase B pathway. A poly(lactide-co-glycolide) nanoparticle (NP) was used to load DL, and the DL-loaded NP was modified with HCC membrane and M2 macrophage-binding peptide (M2pep), forming a nanoformulation (DL@NP-M-M2pep). DL@NP-M-M2pep transformed M2 TAMs to M1 and remodeled the immunosuppressive TME in HCC mice, promoting the efficacy of anti-CD47 antibody for long-term animal survival. These findings reveal a potential TAM modulatory function of DL and provide a combinatorial strategy for HCC immunotherapy.

The OsSGS3-tasiRNA-OsARF3 module orchestrates abiotic-biotic stress response trade-off in rice.

Recurrent heat stress and pathogen invasion seriously threaten crop production, and abiotic stress often antagonizes biotic stress response against pathogens. However, the molecular mechanisms of trade-offs between thermotolerance and defense remain obscure. Here, we identify a rice thermo-sensitive mutant that displays a defect in floret development under high temperature with a mutation in SUPPRESSOR OF GENE SILENCING 3a (OsSGS3a). OsSGS3a interacts with its homolog OsSGS3b and modulates the biogenesis of trans-acting small interfering RNA (tasiRNA) targeting AUXIN RESPONSE FACTORS (ARFs). We find that OsSGS3a/b positively, while OsARF3a/b and OsARF3la/lb negatively modulate thermotolerance. Moreover, OsSGS3a negatively, while OsARF3a/b and OsARF3la/lb positively regulate disease resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) and the fungal pathogen Magnaporthe oryzae (M. oryzae). Taken together, our study uncovers a previously unknown trade-off mechanism that regulates distinct immunity and thermotolerance through the OsSGS3-tasiRNA-OsARF3 module, highlighting the regulation of abiotic-biotic stress response trade-off in plants.

Evaluation of a population-based breast cancer screening in North China.

BACKGROUND: Despite mammography-based screening for breast cancer has been conducted in many countries, there are still little data on participation and diagnostic yield in population-based breast cancer screening in China. METHODS: We enrolled 151,973 eligible women from four cities in Hebei Province within the period 2013-2021 and followed up until December 31, 2021. Participants aged 40-74 who assessed as high risk were invited to undergo breast ultrasound and mammography examination. Overall and group-specific participation rates were calculated. Multivariable analyses were used to estimate the factors associated with participation rates. The diagnostic yield of both screening and no screening groups was calculated. We further analyzed the stage distribution and molecular subtype of breast cancer cases by different modes of cancer detection. RESULTS: A total of 42,547 participants were evaluated to be high risk of breast cancer. Among them, 23,009 subjects undertook screening services, with participation rate of 54.08%. Multivariable logistic regression model showed that aged 45-64, high education level, postmenopausal, current smoking, alcohol consumption, family history of breast cancer, and benign breast disease were associated with increased participation of screening. After median follow-up of 3.79 years, there were 456 breast cancer diagnoses of which 65 were screen-detected breast cancers (SBCs), 27 were interval breast cancers (IBCs), 68 were no screening cancers, and 296 were cancers detected outside the screening program. Among them, 92 participants in the screening group (0.40%) and 364 in the non-screening group (0.28%) had breast cancer detected, which resulted in an odds ratio of 1.42 (95% CI 1.13-1.78; P = 0.003). We observed a higher detection rate of breast cancer in the screening group, with ORs of 2.42 (95% CI 1.72-3.41) for early stage (stages 0-I) and 2.12 (95% CI 1.26-3.54) for luminal A subtype. SBCs had higher proportion of early stage (71.93%) and luminal A subtype (47.22%) than other groups. CONCLUSIONS: The significant differences in breast cancer diagnosis between the screening and non-screening group imply an urgent need for increased breast cancer awareness and early detection in China.