Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity.

The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases.

Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection.

Recent work suggests that cholesterol metabolism impacts innate immune responses against infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we have shown that upon DNA and RNA viral infection, macrophages reduced 7-dehydrocholesterol reductase (DHCR7) expression. DHCR7 deficiency or treatment with the natural product 7-dehydrocholesterol (7-DHC) could specifically promote phosphorylation of IRF3 (not TBK1) and enhance type I interferon (IFN-I) production in macrophages. We further elucidated that viral infection or 7-DHC treatment enhanced AKT3 expression and activation. AKT3 directly bound and phosphorylated IRF3 at Ser385, together with TBK1-induced phosphorylation of IRF3 Ser386, to achieve IRF3 dimerization. Deletion of DHCR7 and the DHCR7 inhibitors including AY9944 and the chemotherapy drug tamoxifen promoted clearance of Zika virus and multiple viruses in vitro or in vivo. Taken together, we propose that the DHCR7 inhibitors and 7-DHC are potential therapeutics against emerging or highly pathogenic viruses.

AKT2 reduces IFNß1 production to modulate antiviral responses and systemic lupus erythematosus.

Interferon regulatory factor 3 (IRF3)-induced type I interferon (I-IFN) production plays key roles in both antiviral and autoimmune responses. IRF3 phosphorylation, dimerization, and nuclear localization are needed for its activation and function, but the precise regulatory mechanisms remain to be explored. Here, we show that the serine/threonine kinase AKT2 interacts with IRF3 and phosphorylates it on Thr207, thereby attenuating IRF3 nuclear translocation in a 14-3-3ε-dependent manner and reducing I-IFN production. We further find that AKT2 expression is downregulated in viral-infected macrophages or in monocytes and tissue samples from systemic lupus erythematosus (SLE) patients and mouse models. Akt2-deficient mice exhibit increased I-IFN induction and reduced mortality in response to viral infection, but aggravated severity of SLE. Overexpression of AKT2 kinase-inactive or IRF3-T207A mutants in zebrafish supports that AKT2 negatively regulates I-IFN production and antiviral response in a kinase-dependent manner. This negative role of AKT2 in IRF3-induced I-IFN production suggests that AKT2 may be therapeutically targeted to differentially regulate antiviral infection and SLE.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

Genome sequences and population genomics reveal climatic adaptation and genomic divergence between two closely related sweetgum species.

Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non-model tree species are not yet fully understood. To address this issue, we generated whole-genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long-term refugial isolation and recent differential introgression in low-recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values.

NLRP3 Phosphorylation Is an Essential Priming Event for Inflammasome Activation.

Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.

Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias. Subsequently, we used quantitative proteomics to find differential proteins in mild, moderate and severe hypospadias. After bioinformatics analysis and biochemical experiments on the screened DEPs, we found that the expression of proteins related to immune inflammation, coagulation, blood pressure and inflammation, and blood lipid were differential expressed in the prepuce tissue of children with hypospadias. We further confirmed that the proteins FGB, FGG, SERPINA1, and AGT involved in the angiotensin system, cholesterol metabolism, and coagulation were significantly up-regulated by biochemical experiments. In particular, the AGT protein of the angiotensin system involved in blood pressure regulation, we have shown that it increases with the severity of hypospadias. This study suggests that children with hypospadias are more likely to suffer from hyperlipidemia and cardiovascular disease (CVD). Our findings provide a theoretical basis for early monitoring of blood lipids and blood pressure to prevent CVD in children with hypospadias.

The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA.

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis.

Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, but the direct comparability of ECs versus concurrent controls is unknown. Objectives: To develop IPF ECs by fit-for-purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the phase II RCT of BMS-986020. Methods: After data curation, the rate of change in FVC from baseline to 26 weeks among participants receiving BMS-986020 600 mg twice daily was compared with the BMS-placebo arm and ECs using mixed-effects models with inverse probability weights. Measurements and Main Results: At 26 weeks, the rates of change in FVC were -32.71 ml for BMS-986020 and -130.09 ml for BMS-placebo (difference, 97.4 ml; 95% confidence interval [CI], 24.6-170.2), replicating the original BMS-986020 RCT. RCT ECs showed treatment effect point estimates within the 95% CI of the original BMS-986020 RCT. Pulmonary Fibrosis Foundation Patient Registry ECs and EHR ECs experienced a slower rate of FVC decline compared with the BMS-placebo arm, resulting in treatment-effect point estimates outside of the 95% CI of the original BMS-986020 RCT. Conclusions: IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, whereas ECs from real-world data sources, including registry or EHR data, do not. RCT ECs may serve as a potentially useful supplement to future IPF RCTs.

Whole genome sequencing of a snailfish from the Yap Trench (~7,000 m) clarifies the molecular mechanisms underlying adaptation to the deep sea.

Hadal environments (depths below 6,000 m) are characterized by extremely high hydrostatic pressures, low temperatures, a scarce food supply, and little light. The evolutionary adaptations that allow vertebrates to survive in this extreme environment are poorly understood. Here, we constructed a high-quality reference genome for Yap hadal snailfish (YHS), which was captured at a depth of ~7,000 m in the Yap Trench. The final YHS genome assembly was 731.75 Mb, with a contig N50 of 0.75 Mb and a scaffold N50 of 1.26 Mb. We predicted 24,329 protein-coding genes in the YHS genome, and 24,265 of these genes were successfully functionally annotated. Phylogenetic analyses suggested that YHS diverged from a Mariana Trench snailfish approximately 0.92 million years ago. Many genes associated with DNA repair show evidence of positive selection and have expanded copy numbers in the YHS genome, possibly helping to maintain the integrity of DNA under increased hydrostatic pressure. The levels of trimethylamine N-oxide (TMAO), a potent protein stabilizer, are much higher in the muscles of YHS than in those of shallow-water fish. This difference is perhaps due to the five copies of the TMAO-generating enzyme flavin-containing monooxygenase-3 gene (fmo3) in the YHS genome and the abundance of trimethylamine (TMA)-generating bacteria in the YHS gut. Thus, the high TMAO content might help YHS adapt to high hydrostatic pressure by improving protein stability. Additionally, the evolutionary features of the YHS genes encoding sensory-related proteins are consistent with the scarce food supply and darkness in the hadal environments. These results clarify the molecular mechanisms underlying the adaptation of hadal organisms to the deep-sea environment and provide valuable genomic resources for in-depth investigations of hadal biology.

Creatine chemical exchange saturation transfer (CEST) CMR imaging reveals myocardial early involvement in idiopathic inflammatory myopathy at 3T: feasibility and initial experience.

OBJECTIVES: To measure creatine distribution in idiopathic inflammatory myopathy (IIM) patients' myocardial segments and investigate whether cardiovascular magnetic resonance (CMR) chemical exchange saturation transfer (CEST) creatine mapping can detect subclinical myocardial changes, CEST's ability was further compared with other conventional CMR mapping sequences. METHODS: Forty IIM patients (53.5 ± 10.5 years, 26 males) and eight healthy controls (35.4 ± 6 years, 5 males) underwent CMR scans on a 3.0-T MR scanner. Patients with IIM were further classified into two subgroups according to cardiac troponin T (cTn-T) values: the elevated cTn-T subgroup (n = 14) and the normal cTn-T subgroup (n = 26). Cine imaging, T2 SPAIR, LGE imaging, T1 mapping, T2 mapping, and Cr (creatine) CEST were performed. RESULTS: Cr mapping showed significantly reduced creatine in IIM patients among global myocardium (IIM: 0.109 ± 0.063, controls: 0.121 ± 0.021, p < 0.05), and decreased creatine signals were detected in all 16 cardiac segments (p < 0.05). Patients also had significantly prolonged native T1 and decreased enhanced T1 values in each cardiac segment (p < 0.05). There was no significant difference of LVEF and T2 values between IIM patients and controls. Between the two subgroups, elevated cTn-T was linked with creatine and extracellular volume fraction (ECV) values, providing a global average creatine signal of 0.107 vs 0.112 (p < 0.05) and 24.7 vs 32.4 (p < 0.05). CONCLUSION: Creatine CEST mapping can detect early-stage heart involvement with negative LGE findings in IIM. Compared with T1 mapping, CEST provides increased sensitivity to ECV measurement, making it significantly better than T1, and a promising CMR sequence for screening subclinical myocardial damage. KEY POINTS: • IIM patients with potential or ongoing heart involvement, elevated ECV, and reduced Cr CEST values could provide valuable information. • ECV and Cr CEST values were closely related to elevated cTn-T.

Highly Tunable MOF Luminophores Featuring Anthracene Directed Assembly and Fluorescence Regulation.

Metal-organic frameworks (MOFs) have been recognized as a potential platform for the development of tunable luminophores owing to their highly modulable structures and components. Herein, two MOF luminophores based on Cd(II) ions, 1,3,5-tri(4-pyridinyl)benzene (TPB), and 1,4-dicarboxybenzene (H2BDC) were constructed. The directed assembly of the metal ions and organic linkers results in [Cd2(BDC)2(TPB)(H2O)]·x(solvent) (MOF-1) featuring TPB-based blue fluorescence centered at 425 nm. By introducing anthracene as the structure directing agent (SDA) for assembly regulation, [Cd2(BDC)(TPB)2(NO3)2]·x(solvent) (MOF-2) was obtained, which reveals anthracene feeding-dependent high tunable emission in the 517-650 nm range. Detailed components, photophysical properties, and structural characteristics investigations of MOF-2 indicate the TPB and NO3- interactions as the origin of its redshifted emission compared with that of MOF-1. Furthermore, the fluorescence of MOF-2 was found to be regulatable by the anthracene feeding based on the SDA-determined crystallinity of the crystalline sample. All these results provided a unique example of the structural and fluorescence regulation of MOF luminophores.

G3BP1 Inhibition Alleviates Intracellular Nucleic Acid-Induced Autoimmune Responses.

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.

Use machine learning to help identify possible sarcopenia cases in maintenance hemodialysis patients.

BACKGROUND: Maintenance hemodialysis (MHD) patients often suffer from sarcopenia, which is strongly associated with their long-term mortality. The diagnosis and treatment of sarcopenia, especially possible sarcopenia for MHD patients are of great importance. This study aims to use machine learning and medical data to develop two simple sarcopenia identification assistant tools for MHD patients and focuses on sex specificity. METHODS: Data were retrospectively collected from patients undergoing MHD and included patients' basic information, body measurement results and laboratory findings. The 2019 consensus update by Asian working group for sarcopenia was used to assess whether a MHD patient had sarcopenia. Finally, 140 male (58 with possible sarcopenia or sarcopenia) and 102 female (65 with possible sarcopenia or sarcopenia) patients' data were collected. Participants were divided into sarcopenia and control groups for each sex to develop binary classifiers. After statistical analysis and feature selection, stratified shuffle split and Synthetic Minority Oversampling Technique were conducted and voting classifiers were developed. RESULTS: After eliminating handgrip strength, 6-m walk, and skeletal muscle index, the best three features for sarcopenia identification of male patients are age, fasting blood glucose, and parathyroid hormone. Meanwhile, age, arm without vascular access, total bilirubin, and post-dialysis creatinine are the best four features for females. After abandoning models with overfitting or bad performance, voting classifiers achieved good sarcopenia classification performance for both sexes (For males: sensitivity: 77.50% ± 11.21%, specificity: 83.13% ± 9.70%, F1 score: 77.32% ± 5.36%, the area under the receiver operating characteristic curves (AUC): 87.40% ± 4.41%. For females: sensitivity: 76.15% ± 13.95%, specificity: 71.25% ± 15.86%, F1 score: 78.04% ± 8.85%, AUC: 77.69% ± 7.92%). CONCLUSIONS: Two simple sex-specific sarcopenia identification tools for MHD patients were developed. They performed well on the case finding of sarcopenia, especially possible sarcopenia.

Advanced materials and technologies for oral diseases.

Oral disease, as a class of diseases with very high morbidity, brings great physical and mental damage to people worldwide. The increasing burden and strain on individuals and society make oral diseases an urgent global health problem. Since the treatment of almost all oral diseases relies on materials, the rapid development of advanced materials and technologies has also promoted innovations in the treatment methods and strategies of oral diseases. In this review, we systematically summarized the application strategies in advanced materials and technologies for oral diseases according to the etiology of the diseases and the comparison of new and old materials. Finally, the challenges and directions of future development for advanced materials and technologies in the treatment of oral diseases were refined. This review will guide the fundamental research and clinical translation of oral diseases for practitioners of oral medicine.

[Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi].

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

[Impact of assisted reproductive technology on birth weight discordance in twins]. / è¾ åŠ©ç”Ÿæ®–æŠ€æœ¯å¯¹åŒèƒŽå‡ºç”Ÿä½“é‡ä¸ä¸€è‡´çš„å½±å“.

OBJECTIVES: To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT). METHODS: A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis. RESULTS: A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05). CONCLUSIONS: ART is not associated with the risk of BWDT.

Genome sequencing and transcriptome analyses provide insights into the origin and domestication of water caltrop (Trapa spp., Lythraceae).

Humans have domesticated diverse species from across the plant kingdom; however, our current understanding of plant domestication is largely founded on major cereal crops. Here, we examine the evolutionary processes and genetic basis underlying the domestication of water caltrop (Trapa spp., Lythraceae), a traditional, yet presently underutilized non-cereal crop that sustained early Chinese agriculturalists. We generated a chromosome-level genome assembly of tetraploid T. natans, and then divided the allotetraploid genome into two subgenomes. Based on resequencing data from 57 accessions, representing cultivated diploid T. natans, wild T. natans (2x and 4x) and diploid T. incisa, we showed that water caltrop was likely first domesticated in the Yangtze River Valley as early as 6300 yr BP, and experienced a second improvement c. 800 years ago. We also provided strong support for an allotetraploid origin of T. natans within the past 230 000-310 000 years. By integrating selective sweep and transcriptome profiling analyses, we identified a number of genes potentially selected and/or differentially expressed during domestication, some of which likely contributed not only to larger fruit sizes but also to a more vigorous root system, facilitating nutrient uptake, environmental stress response and underwater photosynthesis. Our results shed light on the evolutionary and domestication history of water caltrop, one of the earliest domesticated crops in China. This study has implications for genomic-assisted breeding of this presently underutilized aquatic plant, and improves our general understanding of plant domestication.