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Abstract Holobionts are highly organized assemblages of eukaryotic hosts, cellular microbial symbionts, and viruses, whose interactions and evolution involve complex biological processes. It is largely unknown which specific determinants drive similarity or individuality in genetic diversity between holobionts. Here, we combine short- and long-read sequencing and DNA-proximity-linkage technologies to investigate intraspecific diversity of the microbiomes, including host-resolved viruses, in individuals of a model marine sponge. We find strong impacts of the sponge host and the cellular hosts of viruses on strain-level organization of the holobiont, whereas substantial overlap in nucleotide diversity between holobionts suggests frequent exchanges of microbial cells and viruses at intrastrain level in the local sponge population. Immune-evasive arms races likely restricted virus-host co-evolution at the intrastrain level, generated holobiont-specific genome variations, and linked virus-host genetics through recombination. Our work shows that a decoupling of strain- and intrastrain-level interactions is a key factor in the genetic diversification of holobionts.

Background Primary care physicians in community settings face numerous challenges when making medication decisions for patients with multimorbidity. Enhancing their decision-making capabilities through training is an important way to address these challenges. However, there is a dearth of in-depth research on the training needs of primary care physicians in the context of medication decision-making for multimorbidity. Objective This study aims to explore the challenge physicians encountered in medication decision-making for patients with multimorbidity and their needs for training content and modalities, providing a reference for designing the training courses for the abilities enhancement. Methods From October 5th to December 21st in 2023, physicians from community health care centers in Hangzhou, Ningbo, Jiaxing, Shenzhen, and Shanghai were recruited for in-depth interviews following the principle of purposive sampling and maximum variation, which focus on the content and formats of training to enhance medication decision-making abilities. Two researchers transcribed and coded the interviews independently, and content analysis was performed on the interview data. Results A total of 20 Physicians completed the interviews and 15 were females, mean age were (38.5±3.0) years. Based on the challenges faced by primary care physicians in the medication decision-making for multimorbidity, the training should cover four aspects: evaluation of medication therapy, rational selection of medication, doctor-patient communication and shared decision-making, medication education and follow-up. In terms of training form, primary care physicians are willing to accept flexible and multiple teaching approaches, and prefer case-based training that aligns with community health needs. Conclusion Primary care physicians have clear training needs of medication decision-making for patients with multimorbidity. The results of this study provide a theoretical reference for the development of training courses, which adapt to the working environment and actual requirements of primary care physicians.

The accurate understanding of rockburst mechanism poses a global challenge in the field of rock mechanics. Particularly for strain rockburst, achieving self-initiated static-dynamic state transition is a crucial step in the formation of catastrophic events. However, the state transition behavior and its impact on rockburst have not received sufficient attention, and are still poorly understood. Therefore, this study specifically focuses on the state transition behavior, aiming to investigate its abrupt transition process and formation mechanism, and triggering effects on rockburst. To facilitate the study, a novel burst rock-surrounding rock combined laboratory test model is proposed and its effectiveness is validated through experiment verification. Subsequently, corresponding numerical models are established using the three-dimensional (3D) discrete element method (DEM), enabling successful simulation of static brittle failure and rockbursts of varying intensities under quasi-static displacement loading conditions. Moreover, through secondary development, comprehensive recording of the mechanical and energy information pertaining to the combined specimen system and its subsystems is achieved. As a result of numerical investigation studies, the elastic rebound dynamic behavior of the surrounding rock was discovered and identified as the key factor triggering rockburst and controlling its intensity. The impact loading on the burst rock, induced by elastic rebound, directly initiates the dynamic processes of rockburst, serving as the direct cause. Additionally, the transient work and energy convergence towards the burst rock resulting from elastic rebound are recognized as the inherent cause of rockburst. Moreover, it has been observed that a larger extent of surrounding rock leads to a stronger elastic rebound, thereby directly contributing to a more intense rockburst. The findings can provide novel theoretical insights for the exploring of rockburst mechanism and the development of monitoring and prevention techniques.

ABSTRACT Marine biofilms were newly revealed as a giant microbial diversity pool for global oceans. However, the cyanobacterial diversity in marine biofilms within the upper seawater column and its ecological and evolutionary implications remains undetermined. Here, we reconstructed a full picture of modern marine cyanobacteria habitats by re-analyzing 9.3 terabyte metagenomic data sets and 2,648 metagenome-assembled genomes (MAGs). The abundances of cyanobacteria lineages exclusively detected in marine biofilms were up to ninefold higher than those in seawater at similar sample size. Analyses revealed that cyanobacteria in marine biofilms are specialists with strong geographical and environmental constraints on their genome and functional adaption, which is in stark contrast to the generalistic features of seawater-derived cyanobacteria. Molecular dating suggests that the important diversifications in biofilm-forming cyanobacteria appear to coincide with the Great Oxidation Event (GOE), “boring billion” middle Proterozoic, and the Neoproterozoic Oxidation Event (NOE). These new insights suggest that marine biofilms are large and important cyanobacterial factories for the global oceans.IMPORTANCECyanobacteria, highly diverse microbial organisms, play a crucial role in Earth’s oxygenation and biogeochemical cycling. However, their connection to these processes remains unclear, partly due to incomplete surveys of oceanic niches. Our study uncovered significant cyanobacterial diversity in marine biofilms, showing distinct niche differentiation compared to seawater counterparts. These patterns reflect three key stages of marine cyanobacterial diversification, coinciding with major geological events in the Earth's history.

Abstract Objectives The endosymbiosis with Symbiodiniaceae is key to the ecological success of reef-building corals. However, climate change is threatening to destabilize this symbiosis on a global scale. Most studies looking into the response of corals to heat stress and ocean acidification focus on coral colonies. As such, our knowledge of symbiotic interactions and stress response in other stages of the coral lifecycle remains limited. Establishing transcriptomic resources for coral larvae under stress can thus provide a foundation for understanding the genomic basis of symbiosis, and its susceptibility to climate change. Here, we present a gene expression dataset generated from larvae of the coral Pocillopora damicornis in response to exposure to acidification and elevated temperature conditions below the bleaching threshold of the symbiosis. Data description This dataset is comprised of 16 samples (30 larvae per sample) collected from four treatments (Control, High pCO2, High Temperature, and Combined pCO2 and Temperature treatments). Freshly collected larvae were exposed to treatment conditions for five days, providing valuable insights into gene expression in this vulnerable stage of the lifecycle. In combination with previously published datasets, this transcriptomic resource will facilitate the in-depth investigation of the effects of ocean acidification and elevated temperature on coral larvae and its implication for symbiosis.

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host–symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill’s structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host–symbiont interaction and the bivalves' environmental adaption mechanisms.

Preeclampsia is the main cause of maternal and infant mortality and morbidity during pregnancy. Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) and human leukocyte antigen G (HLA-G) play crucial roles in immune tolerance at the maternal-fetal interface. In this case‒control study, 154 maternal–fetal pairs were recruited, including 74 pairs with preeclampsia (56 of 74 pairs from family triads) and 80 pairs with a normal pregnancy (78 of 80 pairs from family triads). SNaPshot technology was used to detect genetic polymorphisms for 7 TagSNPs in the KIR2DL4 and HLA-G genes. Among the fetal HLA-G gene polymorphisms, rs9380142 (A vs. G: OR = 2.802, 95% CI = 1.761–4.458) and rs1063320 (G vs. C: OR = 1.807, 95% CI = 1.144–2.852) differed between the preeclampsia group and the control group. The transmission disequilibrium test (TDT) suggested that the differences in the rs9380142G/A polymorphism in foetuses between preeclampsia triads and control triads were due to differences in transmission from the parents (P = 0.001). There was no significant difference in the distribution of maternal KIR2DL4 alleles or genotype frequency between the preeclampsia group and the control group. Gene‒gene interaction analysis revealed that the combined genotypes of maternal rs649216-CC and fetal rs9380142-GG, maternal rs1051456-CG/GG and fetal rs9380142-GG, maternal rs34785252-CC and fetal rs9380142-AA/GA, and maternal rs34785252-CC/AA and fetal rs9380142-GG were associated with a significantly lower risk of preeclampsia. Therefore, this study suggested that the combination of maternal KIR2DL4 and fetal HLA-G polymorphisms was associated with preeclampsia in a Han Chinese population.

During pregnancy, there is a link between disruption of maternal immune tolerance and preeclampsia, but the molecular mechanisms that regulate maternal and fetal immune tolerance remain unclear. This study employs bioinformatics to identify new markers related to placental immune tolerance and explore their potential role in predicting preeclampsia. Analyzing preeclampsia-related gene expression profiles in the Gene Expression Omnibus (GEO) dataset reveals 211 differentially expressed genes (DEGs) in the placenta, mainly influencing immune cell differentiation and response pathways. Employing weighted gene co-expression network analysis (WGCNA) and lasso regression, four potential target genes (ANKRD37, CRH, LEP, SIGLEC6) are identified for potential prediction of preeclampsia. Validation using the GSE4707 dataset confirmed the diagnostic and predictive potential of these candidate genes. RT-qPCR verified up-regulation in the placenta, while ELISA showed their correlation with immune tolerance factors associated with placental immune tolerance. As a result of this study, identifies potential biomarkers associated with placental immunity and contributes to understanding the molecular mechanism of preeclampsia.

Head-to-tail sequences have been reported in human bocavirus (HBoV) 1-4. To reveal their features and functions, HBoV DNA was screened among respiratory specimens from pediatric patients with an acute respiratory infection (ARI) between April 2020 and December 2022, followed by HBoV genotyping. Head-to-tail sequences were detected using nested PCR, TA cloning, and Sanger sequencing, and these findings were confirmed by mNGS and amplicon sequencing. The secondary structure was predicted using the Mfold web server. The results indicated that head-to-tail sequences were detected in 42 specimens through TA cloning from 351 specimens positive for HBoV1 DNA, yielding 92 sequences into 32 types and 2 categories. Additionally, head-to-tail sequences were detected in 16 specimens by amplicon sequencing, yielding 60 sequences categorized into 23 types. The 374nt type, detected in 13 specimens, contains variants 374a and 374b, which differ in the unpaired loop regions of the palindrome or complementary reverse sequences, implying a switch of template chains during the replication process. The mNGS results in three specimens confirmed the presence of circular genome in copies below 1%. In conclusion, head-to-tail sequences of HBoV1 were common in children with ARI and were highly diverse in length and sequences. The variants may be generated by the switch of the template chain in the rolling-circle replication model.

Protein lysine methyltransferases (PKMT) catalyze methylation of lysine residues on histone tails and non-histone targets. These important post-translational modifications affect the structure and compactness of chromatin, which in turn affects gene expression. There is growing evidence that genetic alterations in PKMT affect the normal expression of PKMT in tissues and thus exert oncogenic or tumor suppressor functions. The expression of PKMT has been found to be associated with the prognosis of tumor patients in a variety of solid tumors. In this review, we summarized the functions of three major PKMT, including EZH2, KMT2 family and SMYD family, and their roles in thyroid carcinoma.

The construction of general practitioner (GP) workforce has tended to be mature over recent years, but the overall insufficient competencies of GPs is still one difficulty to be tackled for the construction of GP workforce. Clinical reasoning plays a central role in connecting various abilities in competency training of GPs in China, which is the key to improving the quality of general medical services. To cultivate the clinical reasoning of GPs, Tongji University offers a compulsory course named Clinical Reasoning in General Practice for general practice master students. The course is framed using the Miller's pyramid framework, includes three parts of core module (containing inquiry ability, physical examination, auxiliary examination and patient-doctor communication) , case module (covering undifferentiated illnesses, chronic disease management, coexistence of multiple diseases, psychosomatic diseases and health management) and practice module (including patient reception practice and medical record writing) , which fully reflect the basic characteristics of GPs' competencies. The course requires 32 credit hours, and is taught in multiple forms, including theory teaching, class discussion, problem-based learning and practical sessions. The effectiveness of course learning is assessed using the objective structured clinical examination, which is divided into four test stations: medical history collection, physical examination, patient-doctor communication and wring SOAP notes. Compared with relevant previous courses with separation between course design and actual community services, this course fully reflects the characteristics of general medicine, and helps students to enhance their competencies via improving the level of clinical reasoning.

The central player for chromosome segregation in both mitosis and meiosis is the macromolecular kinetochore structure, which is assembled by >100 structural and regulatory proteins on centromere DNA. Kinetochores play a crucial role in cell division by connecting chromosomal DNA and microtubule polymers. This connection helps in the proper segregation and alignment of chromosomes. Additionally, kinetochores can act as a signaling hub, regulating the start of anaphase through the spindle assembly checkpoint, and controlling the movement of chromosomes during anaphase. However, the role of various kinetochore proteins in plant meiosis has only been recently elucidated, and these proteins differ in their functionality from those found in animals. In this review, our current knowledge of the functioning of plant kinetochore proteins in meiosis will be summarized. In addition, the functional similarities and differences of core kinetochore proteins in meiosis between plants and other species are discussed, and the potential applications of manipulating certain kinetochore genes in meiosis for breeding purposes are explored.

Abstract Objective The association of the triglyceride-glucose (TyG) index with severe consciousness disturbance and in-hospital mortality in patients with cerebrovascular disease in the intensive care unit (ICU) is unclear. This study aimed to investigate the TyG index’s predictive ability on the severity of impaired consciousness and in-hospital mortality in patients with cerebrovascular disease in the ICU. Method Patients diagnosed with non-traumatic cerebral hemorrhage and cerebral infarction were extracted from the MIMIC-IV database and analyzed as two cohorts. The association between the TyG index and the severity of patients’ impairment of consciousness and in-hospital mortality was analyzed using logistic regression models. Using restricted cubic spline curves, we analyzed potential nonlinear relationships between TyG indices and outcome indicators. receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of the TyG index for outcome indicators. Result The study’s last two cohorts comprised 537 patients with traumatic cerebral hemorrhage and 872 patients with cerebral infarction. TyG index was a significant predictor of the severity of impaired consciousness and in-hospital mortality in patients with cerebrovascular disease, as determined by logistic regression. The risk of severe consciousness impairment and in-hospital mortality increased roughly linearly with increasing TyG index. Conclusion The TyG index was found to be a significant predictor for severe impairment of consciousness and in-hospital death in patients with cerebrovascular disease in the ICU, and it provides some predictive value for the severity of consciousness disturbances and in-hospital mortality in cerebrovascular disease patients.

Estuaries serve as crucial filters for land-based pollutants to the open sea, but there is a lack of information on the migration and fate of organophosphate flame retardants (OPFRs) within estuaries. This study focused on the Pearl River Estuary (PRE) by examining the co-occurrence of OPFRs and their metabolites and quantifying their transport fluxes using a mass balance model. The seawater concentrations of OPFRs and their metabolites exhibited significant seasonal variations (p

High-cadence, multiwavelength observations have continuously revealed the diversity of tidal disruption events (TDEs), thus greatly advancing our knowledge and understanding of TDEs. In this work, we conducted an intensive optical-UV and X-ray follow-up campaign of TDE AT 2023lli and found a remarkable month-long bump in its UV/optical light curve nearly 2 months prior to maximum brightness. The bump represents the longest separation time from the main peak among known TDEs to date. The main UV/optical outburst declines as t ^−4.10 , making it one of the fastest-decaying optically selected TDEs. Furthermore, we detected sporadic X-ray emission 30 days after the UV/optical peak, accompanied by a reduction in the period of inactivity. It is proposed that the UV/optical bump could be caused by the self-intersection of the stream debris, whereas the primary peak is generated by the reprocessed emission of the accretion process. In addition, our results suggest that episodic X-ray radiation during the initial phase of decline may be due to the patched obscurer surrounding the accretion disk, a phenomenon associated with the inhomogeneous reprocessing process. The double TDE scenario, in which two stars are disrupted in sequence, is also a possible explanation for producing the observed early bump and main peak. We anticipate that the multicolor light curves of TDEs, especially in the very early stages, and the underlying physics can be better understood in the near future with the assistance of dedicated surveys such as the deep high-cadence survey of the 2.5 m Wide Field Survey Telescope.