A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

A vicinal oxygen chelate protein facilitates viral infection by triggering the unfolded protein response in Nicotiana benthamiana.

Vicinal oxygen chelate (VOC) proteins are members of an enzyme superfamily with dioxygenase or non-dioxygenase activities. However, the biological functions of VOC proteins in plants are poorly understood. Here, we show that a VOC in Nicotiana benthamiana (NbVOC1) facilitates viral infection. NbVOC1 was significantly induced by infection by beet necrotic yellow vein virus (BNYVV). Transient overexpression of NbVOC1 or its homolog from Beta vulgaris (BvVOC1) enhanced BNYVV infection in N. benthamiana, which required the nuclear localization of VOC1. Consistent with this result, overexpressing NbVOC1 facilitated BNYVV infection, whereas, knockdown and knockout of NbVOC1 inhibited BNYVV infection in transgenic N. benthamiana plants. NbVOC1 interacts with the basic leucine zipper transcription factors bZIP17/28, which enhances their self-interaction and DNA binding to the promoters of unfolded protein response (UPR)-related genes. We propose that bZIP17/28 directly binds to the NbVOC1 promoter and induces its transcription, forming a positive feedback loop to induce the UPR and facilitating BNYVV infection. Collectively, our results demonstrate that NbVOC1 positively regulates the UPR that enhances viral infection in plants.

NtG3BPL1 confers resistance to chilli veinal mottle virus through promoting the degradation of 6K2 in tobacco.

The RNA regulatory network is a complex and dynamic regulation in plant cells involved in mRNA modification, translation, and degradation. Ras-GAP SH3 domain-binding protein (G3BP) is a scaffold protein for the assembly of stress granules (SGs) and is considered an antiviral component in mammals. However, the function of G3BP during virus infection in plants is still largely unknown. In this study, four members of the G3BP-like proteins (NtG3BPLs) were identified in Nicotiana tabacum and the expression levels of NtG3BPL1 were upregulated during chilli veinal mottle virus (ChiVMV) infection. NtG3BPL1 was localized in the nucleus and cytoplasm, forming cytoplasmic granules under transient high-temperature treatment, whereas the abundance of cytoplasmic granules was decreased under ChiVMV infection. Overexpression of NtG3BPL1 inhibited ChiVMV infection and delayed the onset of symptoms, whereas knockout of NtG3BPL1 promoted ChiVMV infection. In addition, NtG3BPL1 directly interacted with ChiVMV 6K2 protein, whereas 6K2 protein had no effect on NtG3BPL1-derived cytoplasmic granules. Further studies revealed that the expression of NtG3BPL1 reduced the chloroplast localization of 6K2-GFP and the NtG3BPL1-6K2 interaction complex was localized in the cytoplasm. Furthermore, NtG3BPL1 promoted the degradation of 6K2 through autophagy pathway, and the accumulation of 6K2 and ChiVMV was affected by autophagy activation or inhibition in plants. Taken together, our results demonstrate that NtG3BPL1 plays a positive role in tobacco resistance against ChiVMV infection, revealing a novel mechanism of plant G3BP in antiviral strategy.

Exploration of a machine learning approach for diagnosing sarcopenia among Chinese community-dwelling older adults using sEMG-based data.

BACKGROUND: In the practical application of sarcopenia screening, there is a need for faster, time-saving, and community-friendly detection methods. The primary purpose of this study was to perform sarcopenia screening in community-dwelling older adults and investigate whether surface electromyogram (sEMG) from hand grip could potentially be used to detect sarcopenia using machine learning (ML) methods with reasonable features extracted from sEMG signals. The secondary aim was to provide the interpretability of the obtained ML models using a novel feature importance estimation method. METHODS: A total of 158 community-dwelling older residents (≥ 60 years old) were recruited. After screening through the diagnostic criteria of the Asian Working Group for Sarcopenia in 2019 (AWGS 2019) and data quality check, participants were assigned to the healthy group (n = 45) and the sarcopenic group (n = 48). sEMG signals from six forearm muscles were recorded during the hand grip task at 20% maximal voluntary contraction (MVC) and 50% MVC. After filtering recorded signals, nine representative features were extracted, including six time-domain features plus three time-frequency domain features. Then, a voting classifier ensembled by a support vector machine (SVM), a random forest (RF), and a gradient boosting machine (GBM) was implemented to classify healthy versus sarcopenic participants. Finally, the SHapley Additive exPlanations (SHAP) method was utilized to investigate feature importance during classification. RESULTS: Seven out of the nine features exhibited statistically significant differences between healthy and sarcopenic participants in both 20% and 50% MVC tests. Using these features, the voting classifier achieved 80% sensitivity and 73% accuracy through a five-fold cross-validation. Such performance was better than each of the SVM, RF, and GBM models alone. Lastly, SHAP results revealed that the wavelength (WL) and the kurtosis of continuous wavelet transform coefficients (CWT_kurtosis) had the highest feature impact scores. CONCLUSION: This study proposed a method for community-based sarcopenia screening using sEMG signals of forearm muscles. Using a voting classifier with nine representative features, the accuracy exceeds 70% and the sensitivity exceeds 75%, indicating moderate classification performance. Interpretable results obtained from the SHAP model suggest that motor unit (MU) activation mode may be a key factor affecting sarcopenia.

Cross-Subject Lifelong Learning for Continuous Estimation From Surface Electromyographic Signal.

The employment of surface electromyographic (sEMG) signals in the estimation of hand kinematics represents a promising non-invasive methodology for the advancement of human-machine interfaces. However, the limitations of existing subject-specific methods are obvious as they confine the application to individual models that are custom-tailored for specific subjects, thereby reducing the potential for broader applicability. In addition, current cross-subject methods are challenged in their ability to simultaneously cater to the needs of both new and existing users effectively. To overcome these challenges, we propose the Cross-Subject Lifelong Network (CSLN). CSLN incorporates a novel lifelong learning approach, maintaining the patterns of sEMG signals across a varied user population and across different temporal scales. Our method enhances the generalization of acquired patterns, making it applicable to various individuals and temporal contexts. Our experimental investigations, encompassing both joint and sequential training approaches, demonstrate that the CSLN model not only attains enhanced performance in cross-subject scenarios but also effectively addresses the issue of catastrophic forgetting, thereby augmenting training efficacy.

T-DNA insertion in Arabidopsis caused coexisting chromosomal inversion and duplication at megabase level.

Agrobacteria-mediated transformation is widely used in plant genetic engineering to introduce exogenous genes and create mutant lines through random T-DNA insertion and gene disruption. When T-DNA fragments are inserted into the plant genome, it could cause chromosomal abnormalities. In this study, we investigated the genetic basis of pleiotropic phenotypes observed in the T-DNA insertion mutant lnc161. We discovered that there are four T-DNA insertions present in the lnc161 genome, which disrupted the genes LNC161 (AT3G05035), AT3G57400, AT5G05630, and AT5G16450, respectively. However, none of these insertions were the causative mutation that leads to the lnc161 phenotypes. Strikingly, through genetic analyses and high throughput sequencing, we found an inversion of about 19.8 Mb sequences between LNC161 and AT3G57400. Moreover, the sequences between AT5G05630 and AT5G16450 (about 3.7 Mb) were translocated from chromosome 5 to chromosome 3, adjacent to the inversion sequences, and were duplicated. This duplication led to an up-regulation of genes expression in this region, potentially resulting in pleiotropic morphological traits in lnc161. Overall, this study provides a case showing complex chromosomal re-arrangement induced by T-DNA insertion.

Experimental study on the deterioration of mechanical properties of sandy mudstone under different water-gas interactions.

Based on the water-rock-gas coupling test system, the work combined the scanning electron microscope and XTDIC 3D full-field strain measurement system. The Brazilian splitting test was performed on four groups of sandy mudstone specimens under contrast (CO), mash-gas soaking (MS), water-mash gas soaking (WM), and water-soaking (WS) conditions. The tensile strength, deformation failure, and microscopic characteristics of fractures were studied to reveal the deterioration mechanism of the tensile properties of sandy mudstone under water-gas coupling. The results showed that the uniaxial tensile strength of sandy mudstone specimens under the three soaking conditions was less than that of the contrast conditions. Compared with specimens in the CO group, the tensile strength of specimens in MS-WS groups was reduced; the WS group decreased the most. Specimens changed from brittle failure to plastic failure after soaking. The decrease rate in strength after the peak was consistent with the change trend in tensile strength. It led to a larger localized deformation zone of specimens and more obvious displacement. The deformation localization zone of the WS group was the broadest, with the most intense displacement. Besides, stress concentration first occurred in the submerged part of the WM group. Fractures expanded in the direction of maximum principal strain. The internal pore structure of sandy mudstone specimens in each group changed after soaking. The average porosity, maximum pore area, and probability entropy of specimens in WS-MS groups increased compared to the CO group. The WS group had the largest reduction and the MS group had the smallest. The pre-peak energy storage capacity of sandy mudstone specimens was gradually weakened. Compared with the CO group, that in the WS-MS groups was reduced. The WS group had the greatest reduction, and the MS group had the smallest. The deterioration effect of water on the interior of sandy mudstone was stronger than that of gas. The work is of great significance for understanding the stability of coal and rocks in closed-pit high-gas mines.

Analysis of brominide disinfection by-products (DBPs) in aquaculture water using ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-tof/MS).

BACKGROUND: halogenic disinfectants have been shown to produce toxic and carcinogenic disinfection by-products in the water disinfection process. Dibromohydantoin (DBDMH) is a commonly used water disinfectant in aquaculture. Aquaculture water has more complex matrix, and the analytical method for disinfection by-products (DBPs) have not been reported. Since the content of DBPs is related to the external conditions such as ultraviolet irradiation, temperatures, pH and humic acid. The semi-target screening method for mainly DBPs based on tracing mass spectrometry fragments of bromide and accurate mass of high resolution mass spectrometry was established by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-tof/MS). Br-DBPs as a important class of DBPs from DBDMH, which quantification analysis methods were developed based on accurate mass of high resolution mass spectrometry. METHODS: through screening method to identify unknown Br-DBPs and quantitative analysis of the typical 4-bromophenol by-product of accurate mass was established. The conditions of the instrument parameters of mass spectrometry and SPE sample preparation procedure in complex real sample were optimized. The high efficiency method was demonstrated for the determination of Br-DBPs with a good linear correlation (R2 = 0.999) in the range of 0.500-200 µg L-1 and limit of detections (LODs) and limit of quantifications (LOQs) were 0.0250 ng L-1 and 0.0834 ng L-1, respectively. CONCLUSION: the developed screening and quantification analytical strategy for Br-DBPs is rapid, accurate and sensitivity applicable for environmental in aquaculture water monitoring.

Toll-like receptor 9 signaling is associated with immune responses to Trypanosoma brucei infection.

Trypanosoma brucei, a causative agent of human and animal trypanosomiasis, regularly switches its major surface antigen to avoid elimination by the immune system. Toll-like receptor 9 (TLR9) is a key modulator for resistance to host-infective trypanosomes; however, the underlying molecular mechanism remains indistinct. Thus, we first approached the issue using Tlr9-mutant mice that render them non-responsive to TLR9 agonists. After infection, T cells in the spleens of Tlr9-mutant mice were analyzed by flow cytometry and a reduction in CD8+, CD4+ T, and NKT cells was observed in Tlr9-mutant mice compared to WT mice. We further found that the responses of inflammatory cytokines in the sera were reduced in Tlr9-mutant mice after T. brucei infection. The underlying molecular mechanism was that T. b. brucei DNA activated TLR9, which consequently upregulated the expression of p38 and ERK/MAPK, resulting in host resistance to trypanosome infection. In conclusion, these findings provide novel insights into the TLR9-mediated host responses to trypanosome infection.

Murine skeletal muscle satellite cells isolation and preliminary study on regulation in immune microenvironment during nurse cells formation of Trichinella spiralis infection.

As an intracellular parasitic nematode, Trichinella spiralis (T. spiralis) can induce the formation of nurse cells (NC) in host muscles and keep it to survive within the NC for an extended period. The formation of NC is similar to muscle cell injury and repair which lead to the arrest of satellite cells in the G2/M phase and build a suitable parasitic environment for the muscle larvae of T. spiralis. However, the molecular mechanisms involved in skeletal muscle repair through skeletal muscle satellite cells (SMSC) and the host immune response during T. spiralis infection have not been fully elucidated. In this study, histopathological examination revealed that the severity of damage increased as the infection progressed in the soleus muscle. SMSCs were isolated from BALB/c mice infected with T. spiralis at 4, 21 and 35 days post-infection (dpi). The immunological characteristics of these cells were analyzed by real-time PCR and flow cytometry (FCM). FCM analysis revealed a notable increase in the expression of B7 homolog 1 (B7-H1) in SMSCs following T. spiralis infection, while conversely, the expression of inducible costimulatory ligand (ICOSL) significantly decreased. Furthermore, real-time PCR results showed that toll like receptor 3 (TLR3) expression in SMSCs of the infected mice was upregulated at 21 dpi. The expression levels of three subtypes (PPARα, PPARß and PPARγ) of peroxisome proliferator-activated receptors (PPARs) also increased in the cells. This study highlights the immunological regulation significance of SMSCs host during T. spiralis infection and suggests that SMSCs actively participant in the local immune response to T. spiralis by regulating the interaction between the parasite and the host.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

All-optical neuromorphic XOR and XNOR operation utilizing a photonic spiking neuron based on a passive add-drop microring resonator.

We propose a concise hardware architecture supporting efficient exclusive OR (XOR) and exclusive NOR (XNOR) operations, by employing a single photonic spiking neuron based on a passive add-drop microring resonator (ADMRR). The threshold mechanism and inhibitory dynamics of the ADMRR-based spiking neuron are numerically discussed on the basis of the coupled mode theory. It is shown that a precise XOR operation in the ADMRR-based spiking neuron can be implemented by adjusting temporal differences within the inhibitory window. Additionally, within the same framework, the XNOR function can also be carried out by accumulating the input power over time to trigger an excitatory behavior. This work presents a novel, to the best of our knowledge, and pragmatic technique for optical neuromorphic computing and information processing utilizing passive devices.

Proteomic and cellular characterization of Omicron breakthrough infections and a third homologous or heterologous boosting vaccination in a longitudinal cohort.

BACKGROUND: The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. METHODS: In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA.2.2 breakthrough infections were enrolled. Serum samples were collected at Days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. RESULTS: The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. CONCLUSION: Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.

Celine, a long interspersed nuclear element retrotransposon, colonizes in the centromeres of poplar chromosomes.

Centromeres in most multicellular eukaryotes are composed of long arrays of repetitive DNA sequences. Interestingly, several transposable elements, including the well-known long terminal repeat (LTR) retrotransposon CRM (centromeric retrotransposon of maize), were found to be enriched in functional centromeres marked by the centromeric histone H3 (CENH3). Here we report a centromeric long interspersed nuclear element (LINE), Celine, in Populus species. Celine has colonized preferentially in the CENH3-associated chromatin of every poplar chromosome, with 84% of the Celine elements localized in the CENH3-binding domains. By contrast, only 51% of the CRM elements were bound to CENH3 domains in Populus trichocarpa. These results suggest different centromere targeting mechanisms employed by Celine and CRM elements. Nevertheless, the high target specificity seems to be detrimental to further amplification of the Celine elements, leading to a shorter life span and patchy distribution among plant species compared to the CRM elements. Using a phylogenetically guided approach we were able to identify Celine-like LINE elements in tea plant (Camellia sinensis) and green ash tree (Fraxinus pennsylvanica). The centromeric localization of these Celine-like LINEs was confirmed in both species. We demonstrate that the centromere targeting property of Celine-like LINEs is of primitive origin and has been conserved among distantly related plant species.

Evolution of a Filling Paste Cementitious System and Impact Patterns of Sulfate Mine Water Erosion on Filling Paste Performance.

To assess the impact of sulfate mine water on filling material performance, an accelerated sulfate erosion process was used to analyze the effects of various erosion concentrations, aging periods, and cation types on the macroscopic properties of the filling paste. These properties encompassed apparent phenomena, mass changes, and alterations in the uniaxial compressive strength. Observations revealed sulfate erosion, causing the formation of white substances and salt crystals on specimen surfaces. Initially, all solution-eroded specimens exhibited increased mass and strength. Over time, specimens in 5 and 10% MgSO4 solutions displayed the first signs of decline, while variations in other solutions were relatively small. Increasing the erosion concentration led to greater variations in mass and strength during the initial erosion phase. Specimens in 5 and 10% MgSO4 solutions initially peaked in mass and compressive strength, followed by a decline, while other filling paste specimens continued slow increases. Under equivalent conditions, the MgSO4 solution exhibited stronger erosion than the Na2SO4 solution. Composite erosion by Na2SO4 and MgSO4 involved initial strengthening and gel pore filling, intermediate expansion and crystallization, and late-stage substantial degradation, with MgSO4 exhibiting a more pronounced and complex impact. Gray relational analysis ranked factors affecting mass and uniaxial compressive strength variations as erosion concentration > erosion ion type > erosion aging period. Correlation degrees for factors influencing mass variations were 0.8822, 0.8714, and 0.4754, while for factors influencing uniaxial compressive strength variations, the correlation degrees were 0.8336, 0.7943, and 0.6125, respectively.

The effects of Atractylodes macrocephala extract BZEP self-microemulsion based on gut-liver axis HDL/LPS signaling pathway to ameliorate metabolic dysfunction-associated fatty liver disease in rats.

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.

Using a deep generation network reveals neuroanatomical specificity in hemispheres.

Asymmetry is an important property of brain organization, but its nature is still poorly understood. Capturing the neuroanatomical components specific to each hemisphere facilitates the understanding of the establishment of brain asymmetry. Since deep generative networks (DGNs) have powerful inference and recovery capabilities, we use one hemisphere to predict the opposite hemisphere by training the DGNs, which automatically fit the built-in dependencies between the left and right hemispheres. After training, the reconstructed images approximate the homologous components in the hemisphere. We use the difference between the actual and reconstructed hemispheres to measure hemisphere-specific components due to asymmetric expression of environmental and genetic factors. The results show that our model is biologically plausible and that our proposed metric of hemispheric specialization is reliable, representing a wide range of individual variation. Together, this work provides promising tools for exploring brain asymmetry and new insights into self-supervised DGNs for representing the brain.

Morphology and phylogeny of Cytospora (Cytosporaceae, Diaporthales) species associated with plant cankers in Tibet, China.

During our biodiversity investigations in Tibet, China, typical Cytospora canker symptoms were observed on branches of hosts Myricariapaniculate, Prunuscerasifera and Sibiraeaangustata. Samples were studied, based on morphological features coupled with multigene phylogenetic analyses of ITS, act, rpb2, tef1 and tub2 sequence data, which revealed two new species (Cytosporamyricicolasp. nov. and C.sibiraeicolasp. nov.) and a known species (C.populina). In addition, Cytosporapopulina is newly discovered on the host Prunuscerasifera and in Tibet.