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Abstract Background Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. Methods In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch’s tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman’s correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. Results It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from − 0.228 to -0.385. Further regression analysis presented β values between − 0.954 and − 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. Conclusions The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. Trial registration NCT05644548, December 1, 2022.

Abstract Background Traditional Chinese medicine (TCM) has been hailed as a rich source of medicine, but many types of herbs and their functions still need to be rapidly discovered and elucidated. HerboChip, a target-based drug screening platform, is an array of different fractions deriving from herbal extracts. This study was designed to identify effective components from TCM that interact with vascular endothelial growth factor (VEGF) as a target using HerboChip. Methods Selected TCMs that are traditionally used as remedies for cancer prevention and wound healing were determined and extracted with 50% ethanol. Biotinylated-VEGF was hybridized with over 500 chips coated with different HPLC-separated fractions from TCM extracts and straptavidin-Cy5 was applied to identify plant extracts containing VEGF-binding fractions. Cytotoxicity of selected herbal extracts and their activities on VEGF-mediated angiogenic functions were evaluated. Results Over 500 chips were screened within a week, and ten positive hits were identified. The interaction of the identified herbal extracts with VEGF was confirmed in cultured endothelial cells. The identified herbs promoted or inhibited VEGF-mediated cell proliferation, migration and tube formation. Results from western blotting analysis demonstrated the identified herbal extracts significantly affected VEGF-triggered phosphorylations of eNOS, Akt and Erk. Five TCMs demonstrated potentiating activities on the VEGF response and five TCMs revealed suppressive activities. Conclusions The current results demonstrated the applicability of the HerboChip platform and systematically elucidated the activity of selected TCMs on angiogenesis and its related signal transduction mechanisms.

Abstract In this paper, we investigate the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1430,1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 , 1950 ) D ( s ) → K π D ( s ) within the perturbative QCD (PQCD) framework. The S-wave two-meson distribution amplitudes (DAs) are introduced to describe the final state interactions of the $$K\pi $$ K π pair, which involve the time-like form factors and the Gegenbauer polynomials. In the calculations, we adopt two kinds of parameterization schemes to describe the time-like form factors: one is the relativistic Breit–Wigner (RBW) formula, which is usually more suitable for the narrow resonances, and the other is the LASS line shape proposed by the LASS Collaboration, which includes both the resonant and nonresonant components. We find that the branching ratios and the direct CP violations for the decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) obtained from those of the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) → K π D ( s ) under the narrow width approximation (NWA) can be consistent well with the previous PQCD results calculated in the two-body framework by assuming that $$K^*_0(1430)$$ K 0 ∗ ( 1430 ) is the lowest lying $$\bar{q} s$$ q ¯ s state, which is the so-called scenario II (SII). We conclude that the LASS parameterization is more suitable to describe the $$K_0^{*}(1430)$$ K 0 ∗ ( 1430 ) than the RBW formula, and the nonresonant components play an important role in the branching ratios of the decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) → K π D ( s ) . In view of the large difference between the decay width measurements for the $$K_0^{*}(1950)$$ K 0 ∗ ( 1950 ) given by BaBar and LASS collaborations, we calculate the branching ratios and the CP violations for the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1950 ) D ( s ) → K π D ( s ) by using two values, $$\Gamma _{K^*_0(1950)}=0.100\pm 0.04$$ Γ K 0 ∗ ( 1950 ) = 0.100 ± 0.04 GeV and $$\Gamma _{K^*_0(1950)}=0.201\pm 0.034$$ Γ K 0 ∗ ( 1950 ) = 0.201 ± 0.034 GeV, besides the two kinds of parameterizations for the resonance $$K^*_0(1950)$$ K 0 ∗ ( 1950 ) . We find that the branching ratios and the direct CP violations for the decays $$B_c \rightarrow K_0^{*}(1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1950 ) D ( s ) → K π D ( s ) have not as large difference between the two parameterizations as the case of decays involving the $$K^*_0(1430)$$ K 0 ∗ ( 1430 ) , especially for the results with $$\Gamma _{K^*_0(1950)}=0.201\pm 0.034$$ Γ K 0 ∗ ( 1950 ) = 0.201 ± 0.034 GeV. The effect of the nonresonant component in the $$K^*_0(1950)$$ K 0 ∗ ( 1950 ) may be not so serious as that in the $$K^*_0(1430)$$ K 0 ∗ ( 1430 ) . The quasi-two-body decays $$B^+_c \rightarrow K^{*+}_0(1430) D^{0} \rightarrow K^0 \pi ^+ D^{0}$$ B c + → K 0 ∗ + ( 1430 ) D 0 → K 0 π + D 0 and $$B^+_c \rightarrow K^{*0}_0(1430) D^{+} \rightarrow K^+ \pi ^- D^{+}$$ B c + → K 0 ∗ 0 ( 1430 ) D + → K + π - D + have large branching ratios, which can reach to the order of $$10^{-4}$$ 10 - 4 and are most likely to be observed in the future LHCb experiments. Furthermore, the branching ratios of the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1950 ) D ( s ) → K π D ( s ) are about one order smaller than those of the corresponding decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) → K π D ( s ) .

ObjectivesSubjective cognitive decline (SCD) as a stage between healthy cognition and early neurocognitive disorders, has been proposed to be helpful in the diagnosis of prodromal neurocognitive disorders. To investigate the prevalence of SCD and the related risk factors on the prevalence.MethodsA cross-sectional study involving 1,120 elderly subjects residing in Baotou, China. From June 2021 to June 2023, the data were gathered by research assistants with training utilizing standardized questionnaires. The following factors were evaluated: subjective cognitive decline, physical and cognitive activity levels, past medical history, demographics, instrumental activities of daily living, and cognitive function. Risk factors of SCD were used chi-square tests and multivariate logistic regression analysis.ResultsThe prevalence of SCD was 43.8%. Permanent residence, marital status, BMI, dietary habits, average sleep duration per night, smoking, diabetes, coronary heart disease, and visual impairment were significantly associated with SCD (p

Hematopoietic stem progenitor cells (HSPCs) are derived from a specialized subset of endothelial cells named hemogenic endothelial cells (HECs) via a process of endothelial-to-hematopoietic transition during embryogenesis. Recently, with the usage of multiple single-cell technologies and advanced genetic lineage tracing techniques, namely, “TIF” approaches that combining transcriptome, immunophenotype and function/fate analyses, massive new insights have been achieved regarding the cellular and molecular evolution underlying the emergence of HSPCs from embryonic vascular beds. In this review, we focus on the most recent advances in the enrichment markers, functional characteristics, developmental paths, molecular controls, and the embryonic site-relevance of the key intermediate cell populations bridging embryonic vascular and hematopoietic systems, namely HECs and pre-hematopoietic stem cells, the immediate progenies of some HECs, in mouse and human embryos. Specifically, using expression analyses at both transcriptional and protein levels and especially efficient functional assays, we propose that the onset of Kit expression is at the HEC stage, which has previously been controversial.

Plants in greenhouses are often exposed to low temperature and low light conditions in the winter, and this has a major effect on flower cultivation. Inoculation of plant growth-promoting rhizobacteria (PGPR) can improve the growth of plants under stress. Here, we examined the effects of Pseudomonas fluorescens on the growth, photosynthesis, chlorophyll fluorescence parameters, and antioxidant enzyme systems of violet plants (Matthiola incana) exposed to normal temperature and normal light intensity (18 °C/11 °C, 500 μmol·m-2·s-1, NN), low temperature and normal light intensity (4 °C/1 °C, 500 μmol·m-2·s-1, LN), normal temperature and low light intensity (18 °C/11°C, 100 μmol·m-2·s-1, NL), and low temperature and low light intensity (4 °C/1 °C, 100 μmol·m-2·s-1, LL). The results showed that the plant height, stem diameter, leaf area, shoot fresh/dry weight, and underground fresh/dry weight of violet inoculated with PGPR were 40%, 17%, 13%, 25%, 41%, 30%, and 38% higher than the control, respectively. In addition, the total root length, mean root diameter, number of root tips, number of bifurcated root tips, and root vigor were 24%, 23%, 14%, 30%, and 21% higher in the inoculated group than in the control group, respectively. PGPR promoted chlorophyll accumulation in plants, and the net photosynthetic rate of violets was 32% higher in plants inoculated with PGPR than in control plants. PGPR also significantly promoted the maximum photochemical conversion efficiency of photosystem II (PSII) and the potential activity of PSII under UV light. After inoculation with PGPR, the content of MDA decreased by 16.8%, and the activities of superoxide dismutase and peroxidase increased by 19.2% and 20.0%, respectively. Therefore, PGPR can promote the growth of violet plants by increasing the photosynthetic capacity, activating the antioxidant enzyme system, and reducing damage induced by exposure to low light intensity.

BackgroundAcupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients.MethodsA single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day’s rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively.DiscussionThis trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2300076180.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.

BackgroundEtomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain.MethodsAdult male Sprague–Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC–MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia.ResultsCompared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration.ConclusionDexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

Abstract Background Lung cancer remains the foremost reason of cancer‐related mortality, with invasion and metastasis profoundly influencing patient prognosis. N‐acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)‐acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non‐small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. Methods We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT‐PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK‐8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient‐derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. Results Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E‐cadherin level whereas decreased N‐cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial‐mesenchymal transition (EMT) pathway. Conclusions Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.

Objectives Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD).Design The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study.Setting The study setting was Xinjiang Medical University Affiliated First Hospital in China.Participants Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI

BackgroundAs one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. ObjectiveWe conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. MethodsWe used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. ResultsFrom 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of –9% (95% CI –10.7% to –7.2%; P

Abstract Complete remission of colorectal cancer (CRC) is still unachievable in the majority of patients by common fractionated radiotherapy, leaving risks of tumor metastasis and recurrence. Herein, clinical CRC samples demonstrated a difference in the phosphorylation of translation initiation factor eIF2α (p‐eIF2α) and the activating transcription factor 4 (ATF4), whose increased expression by initial X‐ray irradiation led to the resistance to subsequent radiotherapy. The underlying mechanism is studied in radio‐resistant CT26 cells, revealing that the incomplete mitochondrial outer membrane permeabilization (iMOMP) triggered by X‐ray irradiation is key for the elevated expression of p‐eIF2α and ATF4, and therefore radio‐resistance. This finding guided to discover that metformin and 2‐DG are synergistic in reversing radio resistance by inhibiting p‐eIF2α and ATF4. Liposomes loaded with metformin and 2‐DG (M/D‐Lipo) are thus prepared for enhancing fractionated radiotherapy of CRC, which achieved satisfactory therapeutic efficacy in both local and metastatic CRC tumors by reversing radio‐resistance and preventing T lymphocyte exhaustion.

The novel weapon hypothesis suggests that allelopathy is an important mechanism for exotic plants to successfully invade native plant communities. Allelochemicals from exotic plants affect both native plants and arbuscular mycorrhizal fungi (AMF) in soil. To explore these effects, we conducted pot experiments using a native plant community comprising of Chenopodium album L., Vitex negundo L., Rhus chinensis Mill., and Acer truncatum Bunge. We incorporated AMF strains (Funneliformis mosseae, Glomus versiforme, and Rhizophagus intraradices in a 1:1:1 volume ratio) into a soil mixture comprising equal volumes of autoclaved field soil and grass ash at five concentrations (0 g L–1, CK; 10 g L–1, LRE; 20 g L–1, NRE; 30 g L–1, MRE; and 40 g L–1, HRE) to investigate the allelopathy of Rhus typhina L. root and its interactions with AMF on the native plant community. Our results indicated that low concentrations of allelochemicals promoted the relative growth rate and leaf nitrogen content in the native plant community, which was attributed to the increased environmental stress that improved the degree of leaf photosynthetic capacity and organic synthesis rate in the native communities. Moreover, allelochemicals with toxicity decreased the colonization rates of AMF. Meanwhile, the presence of allelopathic effects induced a decrease in leaf nitrogen, and allelopathy altered the effects of AMF on the native community. Specifically, the high concentration of allelochemicals altered the positive effect of AMF on the total aboveground biomass of the native plant community to a negative effect, likely by decreasing colonization rates or affecting soil physicochemical properties and the composition of the mycorrhizal communities. Consequently, it is necessary to consider the effects of AMF when testing the roles of allelopathy or the novel weapons hypothesis in biological invasions. Graphical abstract

Background: Limited research has been conducted on the impact of rituximab on immune function and the incidence of side effects in children undergoing combination chemotherapy for aggressive mature B-cell lymphoma/leukemia. Methods: Clinical data from 85 patients with primary pediatric aggressive mature B-cell lymphoma/leukemia, treated according to the Chinese Children's Cancer Group (CCCG)-mature B-cell non-Hodgkin lymphoma (BNHL)-2015 protocol from June 1, 2015, to December 1, 2022, were collected from three tertiary medical centers in China. Patients with pre-existing malignancies or primary immune deficiencies (PIDs) were excluded. Results: Between June 1, 2015, and December 1, 2022, 85 patients (65 [76.5%] boys and 20[23.5%] girls; mean age, 6.95 years) were enrolled, and immune data at baseline during follow-up were analyzed. At the end of chemotherapy, a higher proportion of patients in the R4 group exhibited a decrease in peripheral blood CD3− CD19+ B cells (20[100%] of 20 vs 13[47.8%] of 18, p = 0.04), CD3+ T cells (21[91.3%] of 23 vs 14[60.9%] of 23, p = 0.016), and serum IgM (14[60.9%] of 23 vs 4[17.4%] of 23, p = 0.003) compared to the R3 group. However, these differences were no longer statistically significant six months after chemotherapy administration. The combination of rituximab with AA was associated with a higher incidence of significant thrombocytopenia (49[81.7%] of 60 vs 29[52.7%] of 55, p = 0.001) and infection (35[58.3%] of 60 vs 17[30.9%] of 55, p = 0.003) compared to AA alone. Furthermore, the combination of rituximab with BB was linked to a higher incidence of significant thrombocytopenia (32[52.5%] of 61 vs 31[31.0%] of 100, p = 0.007) compared to BB alone. Conclusions: While the effects of rituximab in combination with intense chemotherapy for childhood aggressive mature B-cell lymphoma/leukemia on children's immune function generally recovers within six months it may still prolong the recovery from immunoglobulinemia, posing a risk of secondary infections. Further studies are required to identify children with potential primary immunodeficiencies.

Laminaria japonica (LJ) is a common seaweed, which has been widely used as functional food and medicine, but its pharmaceutical activities in angiogenic regulation are unclear. Here, different lines of studies provide evidence to the suppressive effects of LJ extract in VEGF-medicated angiogenic function. In cellular level, LJ extract significantly inhibited VEGF-mediated endothelial cell proliferation, migration, invasion and tube formation. For in vivo verification, LJ extract suppressed the VEGF-induced formation of sub-intestinal vessels in zebrafish embryo model. In signalling cascades, LJ extract decreased the amount of phosphorylated VEGF receptor-2, as triggered by VEGF, and subsequently some key related downstream elements were obviously inactivated. In parallel, NO production and ROS formation, as induced by VEGF, were significantly attenuated. Thus, these preclinical findings promoted the possible development of LJ extract as a potential therapeutic agent for prevention and clinical treatment of angiogenesis-related diseases.

Abstract Filterless light-ellipticity-sensitive optoelectronic response generally has low discrimination, thus severely hindering the development of monolithic polarization detectors. Here, we achieve a breakthrough based on a configurable circular-polarization-dependent optoelectronic silent state created by the superposition of two photoresponses with enantiomerically opposite ellipticity dependences. The zero photocurrent and the significantly suppressed noise of the optoelectronic silent state singularly enhance the circular polarization extinction ratio (CPER) and the sensitivity to light ellipticity perturbation. The CPER of our device approaches infinity by the traditional definition. The newly established CPER taking noise into account is 3–4 orders of magnitude higher than those of ordinary integrated circular polarization detectors, and it remains high in an expanded wavelength range. The noise equivalent light ellipticity difference goes below 0.009° Hz−1/2 at modulation frequencies above 1000 Hz by a light power of 281 μW. This scheme brings a leap in developing monolithic ultracompact circular polarization detectors.

This study investigated the effects of dioscorea opposite waste (DOW) on the growth performance, blood parameters, rumen fermentation and rumen microbiota of weaned lambs. Sixty healthy weaned Small-Tailed Han lambs (male, (22.68±2.56) kg initially) were used as the experimental animals. Four levels of concentrate: 0 (control, CON), 10% (DOW1), 15% (DOW2) and 20% (DOW3), were replaced with DOW in the basal diet as experimental treatments. The results showed that lambs fed the DOW2 diet had a higher (P0.05) among DOW groups in average daily weight gain (ADG), and replacing concentrate with DOW linearly or quadratically increased (P

Dilated cardiomyopathy (DCM) is one of the most common primary myocardial diseases. However, to this day, it remains an enigmatic cardiovascular disease (CVD) characterized by ventricular dilatation, which leads to myocardial contractile dysfunction. It is the most common cause of chronic congestive heart failure and the most frequent indication for heart transplantation in young individuals. Genetics and various other factors play significant roles in the progression of dilated cardiomyopathy, and variants in more than 50 genes have been associated with the disease. However, the etiology of a large number of cases remains elusive. Numerous studies have been conducted on the genetic causes of dilated cardiomyopathy. These genetic studies suggest that mutations in genes for fibronectin, cytoskeletal proteins, and myosin in cardiomyocytes play a key role in the development of DCM. In this review, we provide a comprehensive description of the genetic basis, mechanisms, and research advances in genes that have been strongly associated with DCM based on evidence-based medicine. We also emphasize the important role of gene sequencing in therapy for potential early diagnosis and improved clinical management of DCM.

Abstract Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by the groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such as anti‐PD‐1/PD‐L1 antibodies. N4‐acetylcytidine (ac4C) modification, catalyzed by NAT10, is an important posttranscriptional modification of mRNA in cancers. However, its impact on immunological dysregulation and the tumor immunotherapy response in CCa remains enigmatic. Here, a significant increase in NAT10 expression in CCa tissues is initially observed that is clinically associated with poor prognosis. Subsequently, it is found that HOXC8 activated NAT10 by binding to its promoter, thereby stimulating ac4C modification of FOXP1 mRNA and enhancing its translation efficiency, eventually leading to induction of GLUT4 and KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted in increased glycolysis and a continuous increase in lactic acid secretion by CCa cells. The lactic acid‐enriched tumor microenvironment (TME) further contributed to amplifying the immunosuppressive properties of tumor‐infiltrating regulatory T cells (Tregs). Impressively, NAT10 knockdown enhanced the efficacy of PD‐L1 blockade‐mediated tumor regression in vivo. Taken together, the findings revealed the oncogenic role of NAT10 in initiating crosstalk between cancer cell glycolysis and immunosuppression, which can be a target for synergistic PD‐1/PD‐L1 blockade immunotherapy in CCa.

Abstract Background Children with Mycoplasma pneumoniae pneumonia (MPP) are prone to a missed diagnosis at the early stages of the disease, which greatly affects the prognosis of children. In this study, the application value of Mycoplasma pneumoniae (MP) antibody titres and RNA detection for diagnosing MP infection in children with community-acquired pneumonia (CAP) was evaluated. The present study aimed to seek appropriate detection methods and strategies for early rapid diagnosis in children with MPP. Methods A retrospective study was conducted on 563 paediatric patients aged 1 month to 15 years with CAP who were admitted to Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology between July 2021 and February 2022. In all patients, throat swabs were collected for MP-RNA detection (simultaneous amplification and testing, SAT), and paired serum samples were collected for MP total antibody detection (particle agglutination, PA). Results The classification as MPP or non-MPP was based on clinical diagnosis, serum MP antibody titre, and clinical or laboratory evidence of infection by other pathogen(s). Among the 563 patients with pneumonia, 187 patients were in the MPP group, and 376 patients were in the non-MPP group. The Kappa values between the particle agglutination test at different titres (1:80, 1:160) and MP-RNA detection were 0.612 and 0.660 (P 36 m), PA (1:160) was just the opposite, while MP-RNA was slightly better than other age groups in the 13–72 months age group. Conclusions For the diagnosis of MPP in children at the early of the disease, the antibody titre (1:160) parallel MP-RNA should be given preference, and then the disease should be further classified according to the antibody titre level and the age of the child. The combined application of the two detection methods could complement each other and strengthen the advantages, providing reliable laboratory evidence for the clinical diagnosis and timely treatment of MPP. When using the PA method alone to provide a reference standard to clarify MP infection, the differential diagnosis ability of 1:80 for MPP is better than 1:160, especially for children younger than 36 months.

Abstract Angelica sinensis (Oliv.) Diels is an important Chinese medicinal plant. A. sinensis seedlings are grown on an undisturbed alpine meadow soil to ensure the high-quality seedlings, but these soils are disappearing year after year. Thus, selecting a suitable bed soil for A. sinensis seedlings could ensure their long-term sustainability. Using HiSeq sequencing of 16S and 18S marker genes, we investigated the rhizosphere bacterial and fungal microbiotas of the seedlings grown in wheat, astragalus, potato, and angelica-cultivated soils at a geo-authentic habitat. Co-occurrence network analysis, canonical correspondence analysis, Mantel test, and Envfit test were used to examine the relationship between the microbiotas and the surrounding factors. Astragalus-cultivated soils exhibited the following properties: the highest plant weight, the highest neighborhood connectivity in the bacterial network, the highest ratio of positive/negative relationship in both bacterial and fungal networks, the highest relative abundance of the arbuscular mycorrhizal fungi and the ectomycorrhizal fungi, the lowest relative abundance of Rhizoctonia solani, the suitable soil pH, and the close relationship between the rhizosphere microbiotas and the ecological factors. Moreover, each growth stage has its own major drivers in all crop-cultivated soils. Climate temperature and soil pH at 56 days after planting, precipitation at 98 days, and plant weight as well as microbial biomass C and N at 129 days were the major drivers of the bacterial and fungal microbiotas. Overall, the astragalus-cultivated soil was a suitable bed soil for nurturing A. sinensis seedlings to replace the undisturbed alpine meadow soils.

Abstract The free‐space optical communication is regarded as a promising technique for next generation networks. However, all the data are exposed in free space with high risk of being attacked or eavesdropping by unauthorized parties. Here, a bipolar photodetector based on the graphene/GaN heterojunction is demonstrated. The polarity of the UV light photocurrent is opposite to that of the red light photocurrent, which results from the interface state filling effect and hot carrier injection into graphene, verified by Kelvin probe force microscope measurement results. Four stable photocurrent levels are demonstrated with only a single graphene/GaN heterojunction via the photocurrent polarity control, which is employed for a secure capability in conventional optical communication by setting visible and UV light as secret and key information, respectively. The technique provides a new strategy to design photodetectors for information encryption technology.

Coumarin-3-carboxylic acid (3-CCA), previously screened from natural coumarins, was found to possess strong antibacterial activity against Acidovorax citrulli (Ac). In order to further evaluate the activity of this compound against plant bacterial pathogens and explore its potential value as a bactericidal lead compound, the activity of 3-CCA against 14 plant pathogenic bacteria in vitro and in vivo was tested. Results showed that 3-CCA exhibited strong in vitro activities against Ac, Ralstonia solanacearum, Xanthomonas axonopodis pv. manihotis, X. oryzae pv. oryzae, and Dickeya zeae with EC50 values ranging from 26.64 μg/mL to 40.73 μg/mL. Pot experiment results showed that 3-CCA had powerful protective and curative effects against Ac. In addition, the protective efficiency of 3-CCA was almost equivalent to that of thiodiazole copper at the same concentration. The results of SEM and TEM observation and conductivity tests showed that 3-CCA disrupted the integrity of the cell membrane and inhibited polar flagella growth. Furthermore, 3-CCA resulted in reductions in motility and extracellular exopolysaccharide (EPS) production of Ac while inhibiting the biofilm formation of Ac. These findings indicate that 3-CCA could be a promising natural lead compound against plant bacterial pathogens to explore novel antibacterial agents.

Watermelon (Citrullus lanatus) is susceptible to wilt disease caused by Fusarium oxysporum f. sp niveum (FON). AMF colonization alleviates watermelon wilt and regulates the composition of root exudates, but the effects of mycorrhizal watermelon root exudates on watermelon Fusarium wilt is not well understood. Root exudates of watermelon inoculated with AMF (Funeliformis mosseae or Glomus versiformme) were collected in this study. Then the root exudates of control plants and mycorrhizal plants were used to irrigate watermelon in continuous cropping soil, respectively. Meanwhile, the watermelon growth, antioxidant enzyme activity, rhizosphere soil enzyme activities and bacterial community composition, as well as the control effect on FON were analyzed. The results indicated that mycorrhizal watermelon root exudates promoted the growth of watermelon seedlings and increased soil enzyme activities, actinomyces, and the quantity of bacteria in rhizosphere soil. The proportion of Proteobacteria and Bacteroides was decreased, and the proportion of Actinobacteria, Firmicutes, and Chloroflexi in rhizosphere soil was increased when the seedlings were watered with high concentrations of mycorrhizal root exudates. The dominant bacterial genera in rhizosphere soil were Kaistobacter, Rhodanobacter, Thermomonas, Devosia, and Bacillus. The root exudates of mycorrhizal watermelon could reduce the disease index of Fusarium wilt by 6.7–30%, and five ml/L of watermelon root exudates inoculated with F. mosseae had the strongest inhibitory effect on watermelon Fusarium wilt. Our results suggest mycorrhizal watermelon root exudates changed the composition of bacteria and soil enzyme activities in rhizosphere soil, which increase the resistance of watermelon to Fusarium wilt and promoted the growth of plants in continuous cropping soil.

Abstract Background Culex pipiens pallens (Diptera: Culicidae) can survive at low temperature for long periods. Understanding the effects of low-temperature stress on the gut microflora and gene expression levels in Cx. pipiens pallens, as well as their correlation, will contribute to the study of the overwintering mechanism of Cx. pipiens pallens. Methods The gut bacteria were removed by antibiotic treatment, and the survival of Cx. pipiens pallens under low-temperature stress was observed and compared with the control group. Then, full-length 16S rRNA sequencing and the Illumina HiSeq X Ten sequencing platform were used to evaluate the gut microflora and gene expression levels in Cx. pipiens pallens under low-temperature stress. Results Under the low-temperature stress of 7 °C, the median survival time of Cx. pipiens pallens in the antibiotic treatment group was significantly shortened by approximately 70% compared to that in the control group. The species diversity index (Shannon, Simpson, Ace, Chao1) of Cx. pipiens pallens decreased under low-temperature stress (7 °C). Non-metric multidimensional scaling (NMDS) analysis divided all the gut samples into two groups: control group and treatment group. Pseudomonas was the dominant taxon identified in the control group, followed by Elizabethkingia and Dyadobacter; in the treatment group, Pseudomonas was the dominant taxon, followed by Aeromonas and Comamonas. Of the 2417 differentially expressed genes (DEGs), 1316 were upregulated, and 1101 were downregulated. Functional GO terms were enriched in 23 biological processes, 20 cellular components and 21 molecular functions. KEGG annotation results showed that most of these genes were related to energy metabolism-related pathways. The results of Pearson’s correlation analysis showed a significant correlation between the gut microcommunity at the genus level and several DEGs. Conclusions These results suggest that the mechanism of adaptation of Cx. pipiens pallens to low-temperature stress may be the result of interactions between the gut bacterial community and transcriptome. Graphical Abstract

Abstract Background Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. Methods The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at − 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. Conclusions Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653

Abstract Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR‐199a‐5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR‐199a‐5p in myocardial I/R injury remain not well‐studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR‐199a‐5p regulates whether miR‐199a‐5p contributes to ferroptosis‐induced cardiomyocyte death responding to oxygen–glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis‐induced cardiomyocyte death occurs and is accompanied by an increase in miR‐199a‐5p level in OGD/R‐treated H9c2 cells. MiR‐199a‐5p inhibitor ameliorated ferroptosis‐induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe2+ contents, and the up‐regulated glutathione (GSH)/glutathione disulphide (GSSG) ratio as well as glutathione peroxidase 4 (Gpx4) protein expression in H9c2 cells‐exposed to OGD/R, while miR‐199a‐5p mimic had the opposite effects. In addition, OGD/R led to the inhibition of Akt/eNOS signaling pathway, which was also blocked by miR‐199a‐5p inhibitor and aggravated by miR‐199a‐5p mimic. Furthermore, LY294002, an inhibitor of Akt/eNOS signaling pathway, abrogated miR‐199a‐5p inhibitor‐induced the reduction of ferroptosis‐induced cardiomyocyte death. In summary, our findings demonstrated that miR‐199a‐5p plays a central role in stimulating ferroptosis‐induced cardiomyocyte death during ischemic/hypoxic injury via inhibiting Akt/eNOS signaling pathway.

Abstract Background Early metastasis is a key factor contributing to poor breast cancer (BC) prognosis. Circulating tumor cells (CTCs) are regarded as the precursor cells of metastasis, which are ultimately responsible for the main cause of death in BC. However, to date molecular mechanisms underlying CTC formation in BC have been insufficiently defined. Methods RNA-seq was carried out in primary tissues from early-stage BC patients (with CTCs≥5 and CTCs = 0, respectively) and the validation study was conducted in untreated 80 BC patients. Multiple in vitro and in vivo models were used in functional studies. Luciferase reporter, ChIP-seq, CUT&Tag-seq, and GST-pulldown, etc. were utilized in mechanistic studies. CTCs were counted by the CanPatrol™ CTC classification system or LiquidBiospy™ microfluidic chips. ERK1/2 inhibitor SCH772984 was applied to in vivo treatment. Results Highly expressed FOXD1 of primary BC tissues was observed to be significantly associated with increased CTCs in BC patients, particularly in early BC patients. Overexpressing FOXD1 enhanced the migration capability of BC cells, CTC formation and BC metastasis, via facilitating epithelial-mesenchymal transition of tumor cells. Mechanistically, FOXD1 was discovered to induce RalA expression by directly bound to RalA promotor. Then, RalA formed a complex with ANXA2 and Src, promoting the interaction between ANXA2 and Src, thus increasing the phosphorylation (Tyr23) of ANXA2. Inhibiting RalA-GTP form attenuated the interaction between ANXA2 and Src. This cascade culminated in the activation of ERK1/2 signal that enhanced metastatic ability of BC cells. In addition, in vivo treatment with SCH772984, a specific inhibitor of ERK1/2, was used to dramatically inhibit the CTC formation and BC metastasis. Conclusion Here, we report a FOXD1-dependent RalA-ANXA2-Src complex that promotes CTC formation via activating ERK1/2 signal in BC. FOXD1 may serve as a prognostic factor in evaluation of BC metastasis risks. This signaling cascade is druggable and effective for overcoming CTC formation from the early stages of BC.

Abstract Background This study aimed to compare the ability of certain obesity-related indicators to identify metabolic syndrome (MetS) among normal-weight adults in rural Xinjiang. Methods A total of 4315 subjects were recruited in rural Xinjiang. The questionnaire, biochemical and anthropometric data were collected from them. Binary logistic regression was used to analyze the association between the z-score of each index and MetS. The area under the receiver-operating characteristic (ROC) curves were used to compare the diagnostic ability of each index. According to the cut-off value of each index, nomogram models were established and their diagnostic ability were evaluated. Results After adjusting for confounding factors, each indicator in different genders was correlated with MetS. Triglyceride-glucose index (TyG index) showed the strongest association with MetS in both males (OR = 3.749, 95%CI: 3.173–4.429) and females (OR = 3.521,95%CI: 2.990–4.148). Lipid accumulation product (LAP) showed the strongest diagnostic ability in both males (AUC = 0.831, 95%CI: 0.806–0.856) and females (AUC = 0.842, 95%CI: 0.820–0.864), and its optimal cut-off values were 39.700 and 35.065, respectively. The identification ability of the TyG index in different genders (males AUC: 0.817, females AUC: 0.817) was slightly weaker than LAP. Waist-to-height ratio (WHtR) had the similar AUC (males: 0.717, females: 0.747) to conicity index (CI) (males: 0.734, females: 0.749), whereas the identification ability of a body shape index (ABSI) (males AUC: 0.700, females AUC: 0.717) was relatively weak. Compared with the diagnostic ability of a single indicator, the AUC of the male nomogram model was 0.876 (95%CI: 0.856–0.895) and the AUC of the female model was 0.877 (95%CI: 0.856–0.896). The identification ability had been significantly improved. Conclusion LAP and TyG index are effective indicators for identifying MetS among normal-weight adults in rural Xinjiang. Nomogram models including age, CI, LAP, and TyG index can significantly improve diagnostic ability.

Abstract Purpose To explore the association between waist circumference (WC), estimated cardiopulmonary function (eCRF), and cardiovascular disease (CVD) risk in southern Xinjiang. Update the Framingham model to make it more suitable for the southern Xinjiang population. Methods Data were collected from 7705 subjects aged 30–74 years old in Tumushuke City, the 51st Regiment of Xinjiang Production and Construction Corps. CVD was defined as an individual's first diagnosis of non-fatal acute myocardial infarction, death from coronary heart disease, and fatal or non-fatal stroke. The Cox proportional hazards regression analysis was used to analyze the association between WC, eCRF and CVD risk. Restricted cubic spline plots were drawn to describe the association of the two indicators with CVD risk. We update the model by incorporating the new variables into the Framingham model and re-estimating the coefficients. The discrimination of the model is evaluated using AUC, NRI, and IDI metrics. Model calibration is evaluated using pseudo R2 values. Results WC was an independent risk factor for CVD (multivariate HR: 1.603 (1.323, 1.942)), eCRF was an independent protective factor for CVD (multivariate HR: 0.499 (0.369, 0.674)). There was a nonlinear relationship between WC and CVD risk (nonlinear χ2 = 12.43, P = 0.002). There was a linear association between eCRF and CVD risk (non-linear χ2 = 0.27, P = 0.6027). In the male, the best risk prediction effect was obtained when WC and eCRF were added to the model (AUC = 0.763((0.734,0.792)); pseudo R 2 = 0.069). In the female, the best risk prediction effect was obtained by adding eCRF to the model (AUC = 0.757 (0.734,0.779); pseudo R 2 = 0.107). Conclusion In southern Xinjiang, WC is an independent risk factor for CVD. eCRF is an independent protective factor for CVD. We recommended adding WC and eCRF in the male model and only eCRF in the female model for better risk prediction.

Abstract Berberine hydrochloride is the main effective component of Coptis spp. used in Chinese herbal medicine and its underlying molecular mechanisms, responsible for inducing effects in crustacean species, are not fully understood. In this study, the molecular response of the crab Charybdis japonica to berberine hydrochloride exposure was studied using transcriptome sequencing. The survival rate, gene expression and activities of several immune enzymes were measured after berberine hydrochloride treatments, with or without injection of the pathogenic bacterium Aeromonas hydrophila. A total of 962 differentially expressed genes (464 up-regulated and 498 down-regulated) were observed during exposure to 100 mg/L of berberine hydrochloride and in the control group after 48 h. Enrichment analysis revealed that these genes are involved in metabolism, cellular processes, signal transduction and immune functions, indicating that exposure to berberine hydrochloride activated the immune complement system. This bioactive compound simultaneously activated fibrinogen beta (FGB), fibrinogen alpha (FGA), alpha-2-macroglobulin (A2M), kininogen (KNG), fibrinogen gamma chain (FGB), alpha-2-HS-glycoprotein (AHSG), caspase-8 (CASP8), cathepsin L (CTSL), adenylate cyclase 3 (Adcy3) and MMP1. Its action could significantly increase the survival rate of the crabs injected with A. hydrophila and promote the activity of LZM, Caspas8, FGA, ACP and AKP in the hepatopancreas. When A. hydrophila was added, the neutralization of 300 mg/L berberine hydrochloride maximized the activities of Caspas8, LZM, ACP and AKP. Our results provide a new understanding of the potential effects of berberine hydrochloride on the immune system mechanisms in crustaceans.

In aquatic animals, the gut microbiota has a significant function in host health and is impacted by the environmental microbiota. To conveniently monitor, assess and predict aquatic animals’ health, a general and effective microbiota health index (microHI) would be helpful, and the correlation between the aquatic environmental microHI and wildlife gut microHI could be expected. Here, we proposed a general microHI based on the microbial phenotypes of mobile element content, potential pathogenicity and oxidative stress tolerance, and then tested the reliability of the fish gut microHI and its correlation with the environmental microHI in the middle Yangtze River. The results showed that there were positive correlations among the abundance ratios of microbes with the microbial phenotypes of mobile element content, potential pathogenicity and oxidative stress tolerance, suggesting that defining the microHI using the average abundance ratios of microbes without these microbial phenotypes is suitable. Fish gut samples with a lower microHI were more likely to have been obtained from specimens with a disordered microbiota (always means unhealthy host), indicating that the gut microHI has the potential to be used to evaluate the health status of aquatic animals. In the middle Yangtze River, the aquatic environmental microHI had hundred-kilometers-scale high spatial heterogeneity but month-scale low temporal heterogeneity from June to September 2020, and in the section with a low aquatic environmental microHI, the fish gut samples were more likely to have relatively low gut microHIs, indicating that the environmental microHI has the potential to be used to predict the health status of aquatic animals at the community level. The current work initially showed the possibility of using environmental microHI to predict aquatic animals’ health although it was not very exact and precise. We encourage more researches to assess the quantitative relationship between the aquatic environmental microHI and aquatic animal gut microHI.

A 52-year-old Chinese woman was admitted to a cardiac intensive care unit (CCU) due to nausea, vomiting, and dyspnea, which began a day before her hospitalization. Metoprolol succinate and conventional treatment for acute myocardial infarction (AMI) were initially administered to the patient based on electrocardiogram (ECG) findings and elevated cardiac troponin I (cTnI). However, the following day, she developed aggravated nausea, vomiting, fever, sweating, a flushed face, a rapid heart rate, and a significant rise in blood pressure. Furthermore, ultrasonic cardiography (UCG) displayed takotsubo-like changes; nevertheless, ECG indicated inconsistent cTnI peaks with extensive infarction. After coronary computed tomography angiography (CTA) ruled out (AMI), and in conjunction with the uncommon findings, we strongly suspected that the patient had a secondary condition of pheochromocytoma-induced takotsubo cardiomyopathy (Pheo-TCM). In the meanwhile, the use of metoprolol succinate was promptly discontinued. This hypothesis was further supported by the subsequent plasma elevation of multiple catecholamines and contrast-enhanced computed tomography (CECT). After one month of treatment with high-dose Phenoxybenzamine in combination with metoprolol succinate, the patient met the criteria for surgical excision and successfully underwent the procedure. This case report demonstrated that pheochromocytoma could induce TCM and emphasized the significance of distinguishing it from AMI (in the context of beta-blocker usage and anticoagulant management).

Taurine has been proven in many trials to alleviate the symptoms of metabolic associated fatty liver disease. Here its protective effect for hepatic steatosis and modulation of AMP-activated protein kinase and insulin signaling pathway were investigated. Steatotic HepG2 cell established with oleic acid (0.05 mmol/L), treated with taurine (5 mmol/L), dorsomorphin (10 μmol/L) for 24 h. Sprague Dawley rats were divided into regular and high-fat diet (HFD) groups, and their corresponding taurine (70 or 350 mg/kg BW/d) groups, fed for 8 weeks. In steatotic cell, taurine reduced the TG concentration and SREBP-1c, PPARγ, FAS, ACC, SCD1 protein levels, decreased phosphorylation of mTOR, IRS1 (Ser302), increased phosphorylation of AMPKα, LKB1, PI3K, Akt, ACC. While dorsomorphin eliminated taurine's TG-lowering effect. In HFD-fed rats, taurine reduced liver TG, serum TG, ALT, AST, IL-1β, IL-4, TNF-α. The effects of taurine on the main factors of fatty acid synthesis were mostly consistent with cell experiments, and the reduction of microRNAs (451, 33, 291b) was aligned with the improvement in LKB1 and AMPK expression in HFD rats. Taurine alleviated steatosis-induced inhibition of IRS1-PI3K-Akt pathway, but suppressed its positively regulated downstream factor mTOR. In parallel, taurine reduced steatosis by activating LKB1-AMPKα pathway via phosphorylation and no-phosphorylation manner, then inhibiting SREBP-1c directly or by suppressing mTOR phosphorylation.