A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct three-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean and standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Cell-cell communications shape tumor microenvironment and predict clinical outcomes in clear cell renal carcinoma.

BACKGROUND: Cell-cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune escape. Nevertheless, comprehensive investigation of cell-cell communications in the ccRCC (Clear cell renal carcinoma) microenvironment and how this interplay affects prognosis still remains limited. METHODS: Intercellular communications were characterized by single-cell data. Firstly, we employed "CellChat" package to characterize intercellular communications across all types of cells in microenvironment in VHL mutated and non-mutated samples from 8 patients, respectively. And pseudotime trajectory analyses were performed with monocle analyses. Finally clinical prognosis and immunotherapy efficacy with different landscapes of intercellular interplay are evaluated by TCGA-KIRC and immunotherapy cohort. RESULTS: Firstly, the VHL phenotype may be related to the intercellular communication landscape. And trajectory analysis reveals the potential relationship of cell-cell communication molecules with T cells and Myeloid cells differentiation. Furthermore, those molecules also correlate with the infiltration of T cells and Myeloid cells. A tumor cluster with highly expressed ligands was defined by quantitative analysis and transcription factor enrichment analysis, which was identified to be pivotal for intercellular communications in tumor microenvironment. Finally, bulk data indicates bulk that different clusters with different intercellular communications have significant predictive value for prognosis and distinguished immunotherapy efficiency. CONCLUSIONS: The intercellular communication landscapes of VHL wild and VHL mutant ccRCC vary. Intercellular communications within the tumor microenvironment also influence T cell and myeloid cell development and infiltration, as well as predict clinical prognosis and immunotherapy efficacy in ccRCC.

Prediction of Self-Report Cognitive Function for the Symptomatic Remission in Schizophrenia Treated with Amisulpride: a Multicenter, 8-Week Case-Control Study.

This study aimed to determine whether self-report cognitive function is a predictor of symptomatic remission in amisulpride-treated schizophrenia. Patients with DSM-IV schizophrenia diagnoses who received amisulpride treatment, were recruited. Each patient received amisulpride with a flexible-dose strategy of 400-800 mg daily for eight weeks. Remission was defined by a shorter version of the Positive and Negative Symptom Scale(PANSS)criteria, which includes six items (PANSS-6) with scores of less than three in each item(criteria A) or total six scores of less than fourteen(criteria B). Three hundred and three patients completed the study in 15 hospitals in China. By criteria A, 244 (80.5%) achieved symptomatic remission at endpoint, and 258 (85.1%) by criteria B. Duration of illness (DOI) (criteria A: t = 2.31, P = 0.025,criteria B:t = 2.24,p = 0.026) and perceived deficits questionnaire at baseline (PDQ20 Day0) (criteria A: t = 3.32, P = 0.001,criteria B:t = 2.76,p = 0.006) in remission groups were less than that in non-remission groups. Logistic regression analysis took into account sex, age, age-onset, DOI, and PDQ20(Day0), and showed that PDQ20(Day0) was a predictor for symptomatic remission in criteria A (B = - 0.02, P = 0.014) and criteria B (B = - 0.03, P = 0.005). The odds ratio (OR) of achieving remission will be reduced by 2% in criteria A and 3% in criteria B. There were no significant differences in gender composition, age, BMI, education level, age-onset, a daily dose of amisulpride and the percentage of PDQ20 Improvement between remission and nonremission in criteria A or criteria B. Receiver operating characteristic(ROC) curves were found for PDQ20(Day0) to define the precise scores to predict remission of schizophrenia (criteria A:AUC = 0.614, S.E. = 0.041, 95% CI = 0.535-0.694, p = 0.007; criteria B:AUC = 0.633, S.E. = 0.045, 95% CI = 0.545-0.721, p = 0.005). Our data suggest that an early self-report cognitive function in amisulpride-treated schizophrenia is important in predicting for symptomatic remission, the fewer scores of PDQ20 at baseline mean the patients have less daily cognitive difficulty, the more likely the patient is to achieve symptomatic remission.

Diagnostic Accuracy of CEUS LI-RADS for the Characterization of Liver Nodules 20 mm or Smaller in Patients at Risk for Hepatocellular Carcinoma.

Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively (P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively (P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.

Comparative analysis of miniature inverted-repeat transposable elements (MITEs) and long terminal repeat (LTR) retrotransposons in six Citrus species.

BACKGROUND: Miniature inverted-repeat transposable elements (MITEs) and long terminal repeat (LTR) retrotransposons are ubiquitous in plants genomes, and highly important in their evolution and diversity. However, their mechanisms of insertion/amplification and roles in Citrus genome's evolution/diversity are still poorly understood. RESULTS: To address this knowledge gap, we developed different computational pipelines to analyze, annotate and classify MITEs and LTR retrotransposons in six different sequenced Citrus species. We identified 62,010 full-length MITEs from 110 distinguished families. We observed MITEs tend to insert in gene related regions and enriched in promoters. We found that DTM63 is possibly an active Mutator-like MITE family in the traceable past and may still be active in Citrus. The insertion of MITEs resulted in massive polymorphisms and played an important role in Citrus genome diversity and gene structure variations. In addition, 6630 complete LTR retrotransposons and 13,371 solo-LTRs were identified. Among them, 12 LTR lineages separated before the differentiation of mono- and dicotyledonous plants. We observed insertion and deletion of LTR retrotransposons was accomplished with a dynamic balance, and their half-life in Citrus was ~ 1.8 million years. CONCLUSIONS: These findings provide insights into MITEs and LTR retrotransposons and their roles in genome diversity in different Citrus genomes.

[Application of Multimodal Transcranial Ultrasound in SD Rats of Cerebral Ischemic Model at Super Early Stage].

OBJECTIVE: To determine the value of applying multimodal ultrasound (mUS) in SD rats of cerebral ischemic model at super early stage (5-15 min after modeling). METHODS: Fifteen focal cerebral ischemic models were established in SD rats with thinning skulls using the suture method. Gray-scale ultrasound, contrast-enhanced ultrasound, and enhanced color Doppler (CECDUS) were performed before and immediately after the modeling to observe the location of the in-cranial suture, perfusion of the right hemisphere, and color flow signal of the middle cerebral artery and the anterior cerebral artery, respectively.A modified neurological deficit score (mNSS) and 2, 3, 5-triphenyltetrazolium chloride (TTC) stains were obtained three hours later to confirm the successful modeling as the gold standard. The positive rate detected by mUS was compared with the gold standard using McNemar tests. RESULTS: One rat died and 14 rats completed the experiment.mUS imaging detected 71% (10/14) positive signals, no significant difference compared with the gold standard (64%, 9/14) ( P>0.05). A hyperechoic double-line at the bottom of the right brain and focal hypoperfused areas in the right hemisphere were observed by gray scale ultrasound and contrast-enhanced ultrasound in the successfully modeled rats, respectively. The CECDUS found no blood flow in the anterior and middle cerebral arteries. Time intensity curve (TIC) analyses indicated significant changes in peak intensity (PI), area under the curve (AUC), wash in slope (WIS), and time to peak (TTP) after successful modeling. CONCLUSION: Multimodal ultrasound can assess modeling success quickly and accurately immediately after the establishment of ischemic model of SD rats.

Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients.

Host restriction factors and type I interferon are important in limiting HIV and HCV infections, yet the role of HIV, HCV mono- and co-infection in regulating these antiviral genes expression is not clear. In this study, we measured the levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -ß mRNA expression in peripheral blood mononuclear cells of 43 HIV mono-infected, 70 HCV mono-infected and 64 HIV/HCV co-infected patients along with 98 healthy controls. We also quantified HIV and HCV viral loads in mono- and co-infected patients. The results showed that HCV, HIV mono- and co-infection differentially increased TRIM22, APOBEC3G, and IFN-α, -ß mRNA expression while the mRNA expression of TRIMα was upregulated only by HCV-mono infection. HIV/HCV co-infection was associated with higher viral load, compared to either HIV or HCV mono-infection. Additionally, we showed TRIMα and TRIM22 positively correlated with IFN-α, -ß, which could be dysregulated by HIV, HCV mono- and co-infection. Furthermore, we found TRIM22 negatively correlated with HCV viral load in mono-infected patients and APOBEC3G positively correlated with HCV viral load in co-infected patients. Collectively, our findings suggest the potential role of restriction factors in restricting HIV, HCV mono- and co-infection in vivo, which appears to be a therapeutic target for potential drug discovery.

Palladium-Catalyzed Decarboxylative Acylation of N-Nitrosoanilines with α-Oxocarboxylic Acids.

A palladium-catalyzed oxidative C-H bond decarboxylative acylation of N-nitrosoanilines using α-oxocarboxylic acid as the acyl source is described. The catalyst Pd(OAc)2 and oxidant (NH4)2S2O8 enabled ortho-acylation of N-nitrosoanilines at room temperature, affording an array of N-nitroso-2-aminobenzophenones in moderate to excellent yields.

Lipopolysaccharide suppresses human immunodeficiency virus 1 reverse transcription in macrophages.

HIV-1-infected macrophages are long-lived and act as human immunodeficiency virus 1 (HIV-1) virus reservoirs. Lipopolysaccharide (LPS) has been demonstrated to suppress HIV-1 replication in macrophages, but the mechanism is not clear. Previous research suggested that downregulation of CD4 and CCR5 as well as blockage of the interaction of HIV-1 with cells are major causes of inhibition of HIV-1 replication in macrophages by LPS. In order to study whether LPS blocks the post-entry event of HIV-1 replication, we developed a macrophage HIV-1 infection model by using VSV-G pseudotyped HIV-1-luciferase virus to infect THP-1 differentiated macrophage-like cells. We found that LPS can suppress HIV-1 replication at post-entry steps. Further study suggested that HIV-1 reverse transcription was blocked by LPS, but addition of exogenous deoxyribonucleosides led to only partial recovery of HIV-1 replication. However, the inhibition of pro-inflammatory pathway completely rescued HIV-1 replication. Thus, our study shows that LPS can suppress the events of HIV-1 replication post-entry, including reverse transcription, and this restriction is mediated by more than one mechanism.

Independent birth of a novel TRIMCyp in Tupaia belangeri with a divergent function from its paralog TRIM5.

The origin of novel genes and their evolutionary fates are long-standing questions in evolutionary biology. These questions become more complicated for genes conserved across various lineages, such as TRIM5, an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 has been subjected to numerous pathogenic challenges and undergone dynamic evolution, making it an excellent example for studying gene diversification. Previous studies among several species showed that TRIM5 gained genetic and functional novelty in a lineage-specific manner, either through gene duplication or a cyclophilin A retrotransposing into the TRIM5 locus, creating the gene fusion known as TRIM5-Cyclophilin A (TRIMCyp). To date, the general pattern of TRIM5 across the mammalian lineage remains elusive. In this study, we surveyed 36 mammalian genomes to verify a potentially novel TRIM5 pattern that uniquely seems to have occurred in tree shrews (Tupaia belangeri), and found that both gene duplication and retrotransposition worked jointly to form a specific TRIM5/TRIMCyp cluster not found among other mammals. Evolutionary analyses showed that tree shrew TRIMCyp (tsTRIMCyp) originated independently in comparison with previously reported TRIMCyps and underwent strong positive selection, whereas no signal of positive selection was detected for other tree shrew TRIM5 (tsTRIM5) genes. Functional assay results suggest a functional divergence between tsTRIMCyp and its closest paralog TRIM5-4, likely reflecting different fates under diverse evolutionary forces. These findings present a rare example of novel gene origination resulting from a combination of gene duplication, retrotransposition, and exon shuffling processes, providing a new paradigm to study genetic innovations and evolutionary fates of duplicated genes.

A novel biosensor-based microarray assay for the visualized detection of CYP2C19 *2, *3, *4 and *5 polymorphisms.

BACKGROUND: A number of studies have indicated that the conversion of clopidogrel to its active metabolite is reduced in patients who carry the CYP2C19 *2, *3, *4 or *5 loss-of-function allele, resulting in decreased response of platelet to clopidogrel treatment and worse cardiovascular outcome. The aim of this study was to develop a novel biosensor-based microarray to visually detect CYP2C19 polymorphisms. METHODS: The target DNA was amplified from regions flanking the respective alleles using 5'-biotinylated reverse primer, and plasmids were prepared for the respective alleles. High stringency reversed hybridization, horseradish peroxidase-labeled streptavidin reaction, and color development, with multiple washes in different steps, were carried out and the results were recorded with an optical camera. The gene chips were tested for specificity, detection limit, intra- and inter-batch variations using the constructed plasmids. Finally, 88 clinical samples were assayed with this microarray as well as direct sequencing. RESULTS: The results could be seen with the naked eye. Concordance tests indicated that for alleles *2, *3, *4, and *5, the κ values between this assay and plasmids all reached 1.000. The detection limit was 5×10² cells/mL. Concordance test between direct sequencing and the microarray assay using 88 clinical samples gave rise to the κ value of 0.983, and p<0.01, indicating very high concordance. CONCLUSIONS: This novel biosensor-based microarray assay can amplify the signal in situ so that it can be detected by simple instruments or even the naked eyes. It is promising for clinical application in hospital laboratories.

[Research Progress on Pollution Characteristics, Degradation, and Transformation of Typical PPCPs in the Process of Wastewater Treatment].

Pharmaceuticals and personal care products (PPCPs) have received extensive attention as a new type of pollutant inin the 21st century, and the ecological and health risks caused by PPCPs have gradually been recognized by government regulatory agencies. Daily use of PPCPs has led to their frequent detection and high concentrations in the influent, effluent, and sludge of wastewater treatment plants, but traditional wastewater treatment processes can't remove them effectively. Most research about enhancing the removal of PPCPs through microbial degradation, photodegradation, and ozonation is still in the laboratory research stage, and the removal effects are not satisfactory when applied to actual sewage treatment. Therefore, the effective removal of PPCPs from domestic wastewater is a critical technical problem that urgently needs to be studied and solved in the coming years. At present, many scholars do not have a comprehensive understanding about the degradation and transformation behaviors of microbes, ultraviolet, and ozone for typical PPCPs in the wastewater treatment process, so it is necessary to conduct a systematic analysis and discussion. In this study, 16 typical PPCPs frequently detected in sewage treatment plants were selected as research objects through a literature review. The occurrence, removal characteristics, and sludge adsorption properties of typical PPCPs in wastewater treatment plants were analyzed and summarized. The degradation and transformation behavior of typical PPCPs under microbial, ultraviolet, and ozone treatments in the wastewater treatment process were also discussed. Finally, based on current research gaps, some research directions for the removal and transformation of PPCPs in wastewater were proposed:① investigation into the removal characteristics of PPCPs by actual biochemical treatment; ② study on the mechanism of microbial degradation and transformation of typical PPCPs during biochemical treatment; ③ study on the degradation and transformation mechanism of typical PPCPs by UV/ozone in an actual sewage system; and ④ research on the application technology of removing PPCPs from sewage via microbial degradation, photodegradation, ozone oxidation, etc. The relevant results of this study can provide a reference for the pollution control of typical PPCPs in the sewage treatment process.

Two haplotype-resolved genome assemblies for AAB allotriploid bananas provide insights into banana subgenome asymmetric evolution and Fusarium wilt control.

Bananas (Musa spp.) are one of the world's most important fruit crops and play a vital role in food security for many developing countries. Most banana cultivars are triploids derived from inter- and intraspecific hybridizations between the wild diploid ancestor species Musa acuminate (AA) and M. balbisiana (BB). We report two haplotype-resolved genome assemblies of the representative AAB-cultivated types, Plantain and Silk, and precisely characterize ancestral contributions by examining ancestry mosaics across the genome. Widespread asymmetric evolution is observed in their subgenomes, which can be linked to frequent homologous exchange events. We reveal the genetic makeup of triploid banana cultivars and verify that subgenome B is a rich source of disease resistance genes. Only 58.5% and 59.4% of Plantain and Silk genes, respectively, are present in all three haplotypes, with >50% of genes being differentially expressed alleles in different subgenomes. We observed that the number of upregulated genes in Plantain is significantly higher than that in Silk at one-week post-inoculation with Fusarium wilt tropical race 4 (Foc TR4), which confirms that Plantain can initiate defense responses faster than Silk. Additionally, we compared genomic and transcriptomic differences among the genes related to carotenoid synthesis and starch metabolism between Plantain and Silk. Our study provides resources for better understanding the genomic architecture of cultivated bananas and has important implications for Musa genetics and breeding.

Ribosome profiling reveals the translational landscape and allele-specific translational efficiency in rice.

Translational regulation is a critical step in the process of gene expression and governs the synthesis of proteins from mRNAs. Many studies have revealed translational regulation in plants in response to various environmental stimuli. However, there have been no studies documenting the comprehensive landscape of translational regulation and allele-specific translational efficiency in multiple plant tissues, especially those of rice, a main staple crop that feeds nearly half of the world's population. Here we used RNA sequencing and ribosome profiling data to analyze the transcriptome and translatome of an elite hybrid rice, Shanyou 63 (SY63), and its parental varieties Zhenshan 97 and Minghui 63. The results revealed that gene expression patterns varied more among tissues than among varieties at the transcriptional and translational levels. We identified 3392 upstream open reading frames (uORFs), and the uORF-containing genes were enriched in transcription factors. Only 668 of 13 492 long non-coding RNAs could be translated into peptides. Finally, we discovered numerous genes with allele-specific translational efficiency in SY63 and demonstrated that some cis-regulatory elements may contribute to allelic divergence in translational efficiency. Overall, these findings may improve our understanding of translational regulation in rice and provide information for molecular breeding research.

Effect comparisons of different conditioners and microbial agents on the degradation of estrogens during dairy manure composting.

To investigate the degradation efficiency of conditioners and commercial microbial agents on estrogens (E1, 17α-E2, 17ß-E2, E3, EE2, and DES) in the composting process of dairy manure, seven different treatments (RHB-BF, OSP-BF, SD-BF, MR-BF, MR-FS, MR-EM, and MR-CK) under forced ventilation conditions were composted and monitored regularly for 30 days. The results indicated that the removal rates of estrogens in seven treatments ranged from 95.35% to 99.63%, meanwhile the degradation effect of the composting process on 17ß-Estradiol equivalent (EEQ) was evaluated, and the removal rate of ΣEEQ ranged from 96.42% to 99.72%. With the combined addition of rice husk biochar (RHB) or oyster shell powder (OSP) and bio-bacterial fertilizer starter cultures (BF), namely RHB-BF and OSP-BF obviously promoted the rapid degradation of estrogens. 17ß-E2 was completely degraded on the fifth day of composting in OSP-BF. Microbial agents have some promotional effect and enhances the microbial degradation of synthetic estrogen (EE2, DES). According to the results of RDA, pH and EC were the main environmental factors affecting on the composition and succession of estrogen-related degrading bacteria in composting system. As predominant estrogens-degrading genera, Acinetobacter, Bacillus, and Pseudomonas effected obviously on the change of estrogens contents. The research results provide a practical reference for effective composting of dairy manure to enhancing estrogens removal and decreasing ecological risk.

TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR.

Tripartite motif-containing protein 5α (TRIM5α) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5α in the maintenance of viral latency. Knockdown of TRIM5α potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5α. TRIM5α suppresses TNFα-activated HIV-1 LTR-driven as well as NF-κB- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5α binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-κB p50 and Sp1. ChIP‒qPCR analyses further reveal that the association of TRIM5α with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5α orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment.

[Sorption Characteristics and Site Energy Distribution Theory of Typical Estrogens on Microplastics].

Microplastics (MPs) and estrogens are high-profile emerging contaminants at present, and MPs might become the carrier of estrogens in the environment and induce combined pollution. To study the adsorption behavior of polyethylene (PE) microplastics to typical estrogens, the adsorption isothermal properties of the six estrogens[estrone (E1), 17α-estradiol (17α-E2), 17ß-estradiol (17ß-E2), estriol (E3), diethylstilbestrol (DES), and ethinylestradiol (17α-EE2)] in single-solute and mixed-solute systems were studied through batch equilibrium adsorption experiments, in which the PE microplastics before and after adsorption were characterized by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Then, the site energy distribution theory of the adsorption of six estrogens on PE microplastics was further analyzed based on the Freundlich model. The results showed that the adsorption process of selected estrogens with two concentrations (100 µg·L-1 and 1000 µg·L-1) on PE were more consistent with the pseudo-second order kinetic model. The increase in initial concentration reduced the equilibrium time of adsorption and increased the adsorbing capacity of estrogens on PE. In the single system (one estrogen) or mixed system (six estrogens) with different concentrations (10 µg·L-1-2000 µg·L-1), the Freundlich model showed the best fitting effect for the adsorption isotherm data (R2>0.94). The results of isothermal adsorption experiments and XPS and FTIR spectra showed that the adsorption of estrogens on PE in the two systems was heterogeneous adsorption, and hydrophobic distribution and van der Waals forces were the principal factors in the process of adsorption. The occurrence of C-O-C (in only the DES and 17α-EE2 systems) and O-C[FY=,1]O (in only the 17α-EE2 system) indicated that the adsorption of synthetic estrogens on PE was affected slightly by chemical bonding function, but no obvious effects were observed for natural estrogens. The results of site energy distribution analysis showed that, compared with the single system, the adsorption site energy of each estrogen shifted to the high-energy region in its entirety in the mixed system, and the site energy increased by 2.15%-40.98%. The energy change in DES was the most significant among all of the estrogens, indicating its competitive advantage in the mixed system. The above results of this study can provide some reference for the study of adsorption behavior, mechanism of action, and environmental risks under the coexisting condition of organic pollutants and MPs.

Evaluation of febrile seizures in children infected with SARS-CoV-2 Omicron variant in Yunnan, China: a multi-center, retrospective observational study.

Background: The SARS-CoV-2 Omicron variant was reported to be linked to febrile seizures (FSs), but studies on FSs in children with Omicron infection remain relatively scarce, especially in the Chinese population. This study aimed to investigate the characteristics of children diagnosed with Omicron infection with FSs in Yunnan, China, and evaluate the potential association between FSs and Omicron infection. Methods: This study was conducted at four hospitals in Yunnan from December 8, 2022, to January 8, 2023, and consisted of 590 pediatric subjects. According to clinical characteristics, 85, 129 and 376 subjects were divided into the FS-only, Omicron-FS, and Omicron-only groups, respectively. Demographic, clinical and laboratory data were retrospectively collected for analysis. Results: The incidence of FSs in children with Omicron infection was 25.5% (129/505). Older age, stronger male predominance, as well as lower proportions of prior history and family history of seizures were observed in Omicron-FS and Omicron-only groups than in FS-only group, but there were no differences in these four above-mentioned events between these two Omicron-related groups. Compared to FS-only group, Omicron-FS group also had a shorter fever-to-seizure onset duration and more frequent seizures during a single course of fever. Moreover, higher levels of IL-6, TNF-α and ferritin as well as decreased counts of leukocytes and lymphocytes were confirmed in Omicron-FS group than in FS-only and Omicron-only groups. Regarding COVID-19 vaccination status, Omicron-FS group revealed a higher proportion of unvaccinated children and a lower proportion of three-dose vaccination than Omicron-only group. As for clinical outcomes, proportions of mechanical ventilation and intensive care unit admission observed in the two Omicron-related groups were notably higher than those in FS-only group. Meanwhile, Omicron-FS group showed the longest length of hospital stay, followed by Omicron-only group and FS-only group, in order. Finally, all patients but one who died of fulminant myocarditis had been successfully discharged. Conclusions: The incidence of FSs in children with Omicron infection was 25.5% in Yunnan. FSs might be a clinical sign deserving more attention in children with Omicron infection. Furthermore, COVID-19 vaccination is likely to provide effective protection against Omicron-related FSs in children.

Oncogenic activation revealed by FGFR2 genetic alterations in intrahepatic cholangiocarcinomas.

BACKGROUND: Except for gene fusions, FGFR2 genetic alterations in intrahepatic cholangiocarcinomas (ICCs) have received limited attention, leaving patients harboring activating FGFR2 gene mutations with inadequate access to targeted therapies. EXPERIMENTAL DESIGN: We sought to survey FGFR2 genetic alterations in ICC and pan-cancers using fluorescence in situ hybridization and next-generation sequencing. We conducted an analysis of the clinical and pathological features of ICCs with different FGFR2 alterations, compared FGFR2 lesion spectrum through public databases and multicenter data, and performed cellular experiments to investigate the oncogenic potential of different FGFR2 mutants. RESULTS: FGFR2 gene fusions were identified in 30 out of 474 ICC samples, while five FGFR2 genetic alterations aside from fusion were present in 290 ICCs. The tumors containing FGFR2 translocations exhibited unique features, which we designated as the "FGFR2 fusion subtypes of ICC". Molecular analysis revealed that FGFR2 fusions were not mutually exclusive with other oncogenic driver genes/mutations, whereas FGFR2 in-frame deletions and site mutations often co-occurred with TP53 mutations. Multicenter and pan-cancer studies demonstrated that FGFR2 in-frame deletions were more prevalent in ICCs (0.62%) than in other cancers, and were not limited to the extracellular domain. We selected representative FGFR2 genetic alterations, including in-frame deletions, point mutations, and frameshift mutations, to analyze their oncogenic activity and responsiveness to targeted drugs. Cellular experiments revealed that different FGFR2 genetic alterations promoted ICC tumor growth, invasion, and metastasis but responded differently to FGFR-selective small molecule kinase inhibitors (SMKIs). CONCLUSIONS: FGFR2 oncogenic alterations have different clinicopathological features and respond differently to SMKIs.