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Introductionγ-Aminobutyric acid (GABA) type A receptors (GABAARs) are ligand-gated Cl-channels that mediate the bulk of inhibitory neurotransmission in the mature CNS and are targets of many drugs. During cortical development, GABAAR-mediated signals are significantly modulated by changing subunit composition and expression of Cl-transporters as part of developmental processes and early network activity. To date, this developmental evolution has remained understudied, particularly at the level of cortical layer-specific changes. In this study, we characterized the expression of nine major GABAAR subunits and K-Cl transporter 2 (KCC2) in mouse somatosensory cortex from embryonic development to postweaning maturity.MethodsWe evaluated expression of α1-5, β2-3, γ2, and δ GABAAR subunits using immunohistochemistry and Western blot techniques, and expression of KCC2 using immunohistochemistry in cortices from E13.5 to P25 mice.ResultsWe found that embryonic cortex expresses mainly α3, α5, β3, and γ2, while expression of α1, α2, α4, β2, δ, and KCC2 begins at later points in development; however, many patterns of nuanced expression can be found in specific lamina, cortical regions, and cells and structures.DiscussionWhile the general pattern of expression of each subunit and KCC2 is similar to previous studies, we found a number of unique temporal, regional, and laminar patterns that were previously unknown. These findings provide much needed knowledge of the intricate developmental evolution in GABAAR composition and KCC2 expression to accommodate developmental signals that transition to mature neurotransmission.

Fusarium crown rot (FCR) is one of the most important soilborne diseases affecting wheat production. To investigate the diversity of the pathogens causing this disease, 199 diseased wheat samples were collected from 13 cities in Shandong province. In total, 468 isolates were obtained, and from these isolates, 11 Fusarium species were identified based on phylogenetic analyses with the translation elongation factor-1α (TEF-1α), RNA polymerase II largest subunit (RPB1), and RNA polymerase II second largest subunit (RPB2) gene sequences. Of these Fusarium isolates, 283 were identified as Fusarium pseudograminearum and the remaining isolates were identified as Fusarium graminearum (n = 113), Fusarium sinensis (n = 28), Fusarium acuminatum (n = 18), Fusarium incarnatum (n = 13), Fusarium ipomoeae (n = 5), Fusarium flocciferum (n = 3), Fusarium proliferatum (n = 2), Fusarium asiaticum (n = 1), Fusarium culmorum (n = 1), and Fusarium oxysporum (n = 1), suggesting that F. pseudograminearum is the dominant pathogen of FCR of wheat in Shandong province. Pathogenicity tests demonstrated that all 11 Fusarium species could cause typical symptoms of FCR on wheat seedlings. The results of the study indicate that a greater diversity of Fusarium species can cause FCR of wheat in Shandong province than that has been previously reported. This is the first report in the world of Fusarium incarnatum, Fusarium ipomoeae, and Fusarium flocciferum as pathogens causing FCR in wheat.

Wheat is a vital global food crop, yet it faces challenges in saline–alkali soils where Fusarium crown rot significantly impacts growth. Variations in wheat growth across regions are often attributed to uneven terrain. To explore these disparities, we examined well-growing and poorly growing wheat samples and their rhizosphere soils. Measurements included wheat height, root length, fresh weight, and Fusarium crown rot severity. Well-growing wheat exhibited greater height, root length, and fresh weight, with a lower Fusarium crown rot disease index compared to poorly growing wheat. Analysis of rhizosphere soil revealed higher alkalinity; lower nutrient levels; and elevated Na, K, and Ca levels in poorly growing wheat compared to well-growing wheat. High-throughput sequencing identified a higher proportion of unique operational taxonomic units (OTUs) in poorly growing wheat, suggesting selection for distinct fungal species under stress. FUNGuild analysis indicated a higher prevalence of pathogenic microbial communities in poorly growing wheat rhizosphere soil. This study underscores how uneven terrains in saline–alkali soils affect pH, nutrient dynamics, mineral content, wheat health, and rhizosphere fungal community structure.

The acetylation of histone lysine residues regulates multiple life processes, including growth, conidiation, and pathogenicity in filamentous pathogenic fungi. However, the specific function of each lysine residue at the N-terminus of histone H3 in phytopathogenic fungi remains unclear. In this study, we mutated the N-terminal lysine residues of histone H3 in Fusarium pseudograminearum, the main causal agent of Fusarium crown rot of wheat in China, which also produces deoxynivalenol (DON) toxins harmful to humans and animals. Our findings reveal that all the FpH3K9R, FpH3K14R, FpH3K18R, and FpH3K23R mutants are vital for vegetative growth and conidiation. Additionally, FpH3K14 regulates the pathogen’s sensitivity to various stresses and fungicides. Despite the slowed growth of the FpH3K9R and FpH3K23R mutants, their pathogenicity towards wheat stems and heads remains unchanged. However, the FpH3K9R mutant produces more DON. Furthermore, the FpH3K14R and FpH3K18R mutants exhibit significantly reduced virulence, with the FpH3K18R mutant producing minimal DON. In the FpH3K9R, FpH3K14R, FpH3K18R, and FpH3K23R mutants, there are 1863, 1400, 1688, and 1806 downregulated genes, respectively, compared to the wild type. These downregulated genes include many that are crucial for growth, conidiation, pathogenicity, and DON production, as well as some essential genes. Gene ontology (GO) enrichment analysis indicates that genes downregulated in the FpH3K14R and FpH3K18R mutants are enriched for ribosome biogenesis, rRNA processing, and rRNA metabolic process. This suggests that the translation machinery is abnormal in the FpH3K14R and FpH3K18R mutants. Overall, our findings suggest that H3 N-terminal lysine residues are involved in regulating the expression of genes with important functions and are critical for fungal development and pathogenicity.

Abstract Introduction Acute postoperative pain is a major concern among surgical patients. Thus, this study established a new acute pain management model and compared the effects of the acute pain service (APS) model in 2020 and the virtual pain unit (VPU) model in 2021 on postoperative analgesia quality. Methods This retrospective, single-center clinical study involved 21,281 patients from 2020 to 2021. First, the patients were grouped on the basis of their pain management model (APS and VPU). The incidence of moderate to severe postoperative pain (MSPP) [numeric rating scale (NRS) score ≥ 5], postoperative nausea and vomiting (PONV), and postoperative dizziness were recorded. Results The VPU group recorded significantly lower MSPP incidence (1–12 months), PONV, and postoperative dizziness (1–10 months and 12 months) compared with the APS group. In addition, the annual average incidence of MSPP, PONV, and postoperative dizziness in the VPU group was significantly lower than in the APS group. Conclusions The VPU model reduces the incidence of moderate to severe postoperative pain, nausea, vomiting, and dizziness; hence, it is a promising acute pain management model.

Abstract Chemotherapy was the main treatment method for esophageal cancer (EC) patients. However, chemotherapy resistance due to multiple factors is a major barrier to EC treatment. For investigating how small nucleolar RNA host gene 6 (SNHG6) affected the 5-fluorouracil (5-FU) resistance in EC as well as its possible molecular mechanism. This work conducted cell viability assay, clone formation, scratch assays together with cell apoptosis for evaluating the roles of SNHG6 and enhancer of zeste homolog 2 (EZH2, the histone-lysine N-methyltransferase). Relevant molecular mechanism was identified by RT-qPCR analysis together with Western-blot (WB) assays. Our data showed that SNHG6 expression increased in EC cells. SNHG6 promotes colony formation and migration, whereas suppresses EC cell apoptosis. SNHG6 silencing markedly promoted 5-FU-mediated suppression on KYSE150 and KYSE450 cells. Additional mechanism studies showed that SNHG6 modulating STAT3 and H3K27me3 via promoting EZH2 level. Similar to the function of SNHG6, abnormal expression of EZH2 promotes the malignancy of EC and intensifies its resistance to 5-FU. In addition, overexpression of EZH2 abolished the role of SNHG6 silencing in 5-FU sensitivity in EC cells. SNHG6 overexpression promoted malignancy of EC and increased EC cell resistance to 5-FU. Besides, further molecular mechanism studies provided a novel regulatory pathways that SNHG6 knockdown promoted EC cell sensitivity to 5-FU by modulating STAT3 and H3K27me3 via promoting EZH2 expression.

BackgroundRecurrence of atrial fibrillation (AF) after catheter ablation (CA) remains a challenge today. Although it is believed that evaluating the structural and functional remodeling of the left atrium (LA) may be helpful in predicting AF recurrence, there is a lack of consensus on prediction accuracy. Ultrasound-based radiomics is currently receiving increasing attention because it might aid in the diagnosis and prognosis prediction of AF recurrence. However, research on LA ultrasound radiomics is limited.ObjectiveWe aim to investigate the incremental predictive utility of LA radiomics and construct a radiomics nomogram to preoperatively predict AF recurrence following CA.MethodsA training cohort of 232 AF patients was designed for nomogram construction, while a validation cohort (n = 100) served as the model performance test. AF recurrence during a follow-up period of 3–12 months was defined as the endpoint. The radiomics features related to AF recurrence were extracted and selected to create the radiomics score (rad score). These rad scores, along with other morphological and functional indicators for AF recurrence, were included in the multivariate Cox analysis to establish a nomogram for the prediction of the likelihood of AF recurrence within 1 year following CA.ResultsIn the training and validation cohorts, AF recurrence rates accounted for 32.3% (75/232) and 25.0% (25/100), respectively. We extracted seven types of radiomics features associated with AF recurrence from apical four-chamber view echocardiography images and established a rad score for each patient. The radiomics nomogram was built with the rad score, AF type, left atrial appendage emptying flow velocity, and peak atrial longitudinal strain. It outperformed the nomogram building without the rad score in terms of the predictive efficacy of CA outcome and showed favorable performance in both cohorts.ConclusionWe revealed the incremental utility of a radiomics signature in the prediction of AF recurrence and preliminarily developed and validated a radiomics nomogram for identifying patients who were at high risk of post-CA recurrence, which contributed to an appropriate management strategy for AF.

Biological seed dressing is a cost-effective means to protect plant roots from pathogens. Trichoderma is generally considered as one of the most common biological seed dressings. However, there is still a dearth of information on the effects of Trichoderma on microbial community of rhizosphere soil. High-throughput sequencing was used to analyze the effects of Trichoderma viride and a chemical fungicide on microbial community of soybean rhizosphere soil. The results showed that both T. viride and chemical fungicide could significantly reduce the disease index of soybean (15.11% for Trichoderma and 17.33% for Chemical), while no significant difference was observed between them. Both T. viride and chemical fungicide could affect the structure of rhizosphere microbial community, they increased the β-diversity of microbial community and significantly reduce the relative abundance of Saprotroph-Symbiotroph. Chemical fungicide could reduce the complexity and stability of co-occurrence network. However, T. viride is beneficial for maintaining network stability and increasing network complexity. There were 31 bacterial genera and 21 fungal genera significantly correlated with the disease index. Furthermore, several potential plant pathogenic microorganisms were also positively correlated with disease index, such as Fusarium, Aspergillus, Conocybe, Naganishia, and Monocillium. From this work, T. viride may be used as a substitute for chemical fungicide to control soybean root rot and be more friendly to soil microecology.

Abstract Developing full‐spectrum photocatalysts with simultaneous broadband light absorption, excellent charge separation, and high redox capabilities is becoming increasingly significant. Herein, inspired by the similarities in crystalline structures and compositions, a unique 2D–2D Bi4O5I2/BiOBr:Yb3+,Er3+ (BI‐BYE) Z‐scheme heterojunction with upconversion (UC) functionality is successfully designed and fabricated. The co‐doped Yb3+ and Er3+ harvest near‐infrared (NIR) light and then convert it into visible light via the UC function, expanding the optical response range of the photocatalytic system. The intimate 2D–2D interface contact provides more charge migration channels and enhances the Förster resonant energy transfer of BI‐BYE, leading to significantly improved NIR light utilization efficiency. Density functional theory (DFT) calculations and experimental results confirm that the Z‐scheme heterojunction is formed and that this heterojunction endows the BI‐BYE heterostructure with high charge separation and strong redox capability. Benefit from these synergies, the optimized 75BI‐25BYE heterostructure exhibits the highest photocatalytic performance for Bisphenol A (BPA) degradation under full‐spectrum and NIR light irradiation, outperforming BYE by 6.0 and 5.3 times, respectively. This work paves an effective approach for designing highly efficient full‐spectrum responsive Z‐scheme heterojunction photocatalysts with UC function.

This study aimed to explore the impact of ozonated water (OW) disinfestation on soil fungal community composition in continuous ginger field. All soil samples were collected in continuous ginger field. There were two groups and 5 time points (0, 1, 3, 5, 9 day) in our study, including OW disinfestation treatment group (O3 group) and control group (CK group). Via internal transcribed spacer (ITS) sequencing and further analysis, the changes of fungal community composition were determined. As a result, at 0 and 9 days after aeration, the operational taxonomic units (OTUs) in O3 group were significantly higher than that in CK group. Compared with the CK group, in O3 group: the ACE and Chao1 index significantly increased on day 1, and the Shannon index significantly decreased while Simpson index significantly increased on day 0 after aeration. In O3 group, there were dynamic changes of top 10 abundance fungi from the genus-level and the growth of Trichoderma and Rhodotorula had been promoted while Hannaella was inhibited. In conclusion, OW disinfestation had complicated impacts on fungal communities in continuous ginger fields. The growth of Trichoderma and Rhodotorula has been promoted during disinfestation, which provided more reference information for soil OW disinfestation research.

Lujo virus (LUJV) belongs to the Old World (OW) genus Mammarenavirus (family Arenaviridae). It is categorized as a biosafety level (BSL) 4 agent. Currently, there are no U.S. Food and Drug Administration (FDA)-approved drugs or vaccines specifically for LUJV or other pathogenic OW mammarenaviruses. Here, a high-throughput screening of an FDA-approved drug library was conducted using pseudotype viruses bearing LUJV envelope glycoprotein (GPC) to identify inhibitors of LUJV entry. Three hit compounds, trametinib, manidipine, and lercanidipine, were identified as LUJV entry inhibitors in the micromolar range. Mechanistic studies revealed that trametinib inhibited LUJV GPC-mediated membrane fusion by targeting C410 [located in the transmembrane (TM) domain], while manidipine and lercanidipine inhibited LUJV entry by acting as calcium channel blockers. Meanwhile, all three hits extended their antiviral spectra to the entry of other pathogenic mammarenaviruses. Furthermore, all three could inhibit the authentic prototype mammarenavirus, lymphocytic choriomeningitis virus (LCMV), and could prevent infection at the micromolar level. This study shows that trametinib, manidipine, and lercanidipine are candidates for LUJV therapy and highlights the critical role of calcium in LUJV infection. The presented findings reinforce the notion that the key residue(s) located in the TM domain of GPC provide an entry-targeted platform for designing mammarenavirus inhibitors.

Lassa virus (LASV) is a highly pathogenic virus that is categorized as a biosafety level-4 pathogen. Currently, there are no approved drugs or vaccines specific to LASV. In this study, high-throughput screening of a fragment-based drug discovery library was performed against LASV entry using a pseudotype virus bearing the LASV envelope glycoprotein complex (GPC). Two compounds, F1920 and F1965, were identified as LASV entry inhibitors that block GPC-mediated membrane fusion. Analysis of adaptive mutants demonstrated that the transient mutants L442F and I445S, as well as the constant mutant F446L, were located on the same side on the transmembrane domain of the subunit GP2 of GPC, and all the mutants conferred resistance to both F1920 and F1965. Furthermore, F1920 antiviral activity extended to other highly pathogenic mammarenaviruses, whereas F1965 was LASV-specific. Our study showed that both F1920 and F1965 provide a potential backbone for the development of lead drugs for preventing LASV infection.

Retrospective studies suggest that chimeric antigen receptor T-cell (CAR T) therapy may lead to cardiac injury, but this has not been assessed systematically or prospectively. In this prospective study of 40 patients who received CAR T, we systematically measured high-sensitivity troponin T (hsTropT) and N-terminal pro-B natriuretic peptide (NTproBNP) at baseline and on day 1, days 7, and 21 after CAR T. Biomarker elevations with respect to timepoint and cytokine release syndrome (CRS) status were examined using repeated measure analysis of variance. hsTropT did not differ with time or with the presence of grade 2 CRS. Median hsTropT was 12.1 ng/L [interquartile range (IQR): 9.2, 20.1] at baseline, 13.1 ng/L (IQR: 9.6, 24.2) at day 1, 11.9 ng/L (IQR: 9.6, 18.0) at day 7, and 15.3 ng/L (10.8, 20.2) at day 21. In contrast, NTproBNP rose on day 1 (PWilcox = 0.0002) and day 7 (PWilcox = 2.7 × 10−5), and the degree of elevation differed by the presence of grade 2 CRS (Pinteraction = 0.002). Median NTproBNP was 179 pg/mL (IQR: 116, 325) at baseline, 357 pg/mL (IQR: 98, 813) at day 1, 420 pg/mL (IQR: 239, 1242) at day 7, and 177 pg/mL (IQR: 80, 278) at day 21. In conclusion, hsTropT l did not differ across timepoints after CAR T therapy, but NTproBNP rose at day 7, the prognostic implications of which should be the target of future research, as the indications for this therapy expand.

An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted global health. There is a severe lack of specific treatment options for diseases caused by SARS-CoV-2. In this study, we used a pseudotype virus (pv) containing the SARS-CoV-2 S glycoprotein to screen a botanical drug library containing 1037 botanical drugs to identify agents that prevent SARS-CoV-2 entry into the cell. Our study identified four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, as effective SARS-CoV-2 S pv entry inhibitors in the micromolar range. A mechanistic study revealed that these four agents inhibited SARS-CoV-2 S pv entry by blocking spike (S) protein-mediated membrane fusion. Furthermore, angeloylgomisin O and schisandrin B inhibited authentic SARS-CoV-2 with a high selective index (SI; 50% cytotoxic concentration/50% inhibition concentration). Our drug combination studies performed in cellular antiviral assays revealed that angeloylgomisin O has synergistic effects in combination with remdesivir, a drug widely used to treat SARS-CoV-2-mediated infections. We also showed that two hits could inhibit the newly emerged alpha (B.1.1.7) and beta (B.1.351) variants. Our findings collectively indicate that angeloylgomisin O and schisandrin B could inhibit SARS-CoV-2 efficiently, thereby making them potential therapeutic agents to treat the coronavirus disease of 2019.

Aims. To investigate a new method of left atrial appendage occlusion without fluoroscopy. Methods and Results. We performed left atrial appendage occlusion for 14 patients with atrial fibrillation in our hospital. All of the surgeries were completed in a general surgery setting, avoiding fluoroscopy, and in each case, the entire procedure was guided by transesophageal echocardiography (TEE). All of the surgeries were performed through the femoral vein pathway. All operations went smoothly with no serious complications. Postoperative TEE indicated that each device was in a good position, and there was no residual shunt around any of the devices. Conclusions. TEE-guided left atrial appendage occlusion is safe and reliable, simplifies the procedure, protects doctors and patients from radiation, and is gradually becoming the mainstream operation for left atrial appendage occlusion. This trial is registered with ChiCTR1800018387.

Introduction: γ-Aminobutyric acid (GABA) type A receptors (GABAARs) are ligand-gated Cl-channels that mediate the bulk of inhibitory neurotransmission in the mature CNS and are targets of many drugs. During cortical development, GABAAR-mediated signals are significantly modulated by changing subunit composition and expression of Cl-transporters as part of developmental processes and early network activity. To date, this developmental evolution has remained understudied, particularly at the level of cortical layer-specific changes. In this study, we characterized the expression of nine major GABAAR subunits and K-Cl transporter 2 (KCC2) in mouse somatosensory cortex from embryonic development to postweaning maturity. Methods: We evaluated expression of α1-5, β2-3, γ2, and δ GABAAR subunits using immunohistochemistry and Western blot techniques, and expression of KCC2 using immunohistochemistry in cortices from E13.5 to P25 mice. Results: We found that embryonic cortex expresses mainly α3, α5, β3, and γ2, while expression of α1, α2, α4, β2, δ, and KCC2 begins at later points in development; however, many patterns of nuanced expression can be found in specific lamina, cortical regions, and cells and structures. Discussion: While the general pattern of expression of each subunit and KCC2 is similar to previous studies, we found a number of unique temporal, regional, and laminar patterns that were previously unknown. These findings provide much needed knowledge of the intricate developmental evolution in GABAAR composition and KCC2 expression to accommodate developmental signals that transition to mature neurotransmission. [ABSTRACT FROM AUTHOR]