Biventricular Impairment and Ventricular Interdependence in Patients With Alcoholic Cardiomyopathy: Insights Through Cardiac Magnetic Resonance Imaging.

BACKGROUND: Alcoholic cardiomyopathy (ACM) can lead to progressive cardiac dysfunction and heart failure, but little is known about biventricular impairment and ventricular interdependence (VI) in ACM patients. PURPOSE: To use cardiac MRI to investigate biventricular impairment and VI in ACM patients. STUDY TYPE: Retrospective. POPULATION: Forty-one male patients with ACM and 45 sex- and age-matched controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence, inversion recovery prepared echo-planar imaging sequence and phase-sensitive inversion recovery sequence. ASSESSMENT: Biventricular structure, function, and global strain (encompassing peak strain [PS], peak systolic, and diastolic strain rate), PS of interventricular septal (IVS), microvascular perfusion (including upslope and time to maximum signal intensity [TTM]), late gadolinium enhancement (LGE), and baseline characteristics were compared between the controls and ACM patients. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, Pearson's correlation, and multivariable linear regression models with a stepwise selection procedure. A two-tailed P value <0.05 was deemed as statistically significant. RESULTS: Compared to control subjects, ACM patients showed significantly biventricular adverse remodeling, reduced left ventricle (LV) global upslope and prolonged global TTM, and the presence of LGE. ACM patients were characterized by a significant decline in all global strain within the LV, right ventricle (RV), and IVS compared with the controls. RV global PS was significantly associated with LV global PS and IVS PS in radial, circumferential, and longitudinal directions. Multivariable analyses demonstrated the longitudinal PS of IVS was significantly correlated with RV global radial PS (ß = 0.614) and circumferential PS (ß = 0.545). Additionally, RV global longitudinal PS (GLPS) was significantly associated with radial PS of IVS (ß = -0.631) and LV GLPS (ß = 1.096). DATA CONCLUSION: ACM patients exhibited biventricular adverse structural alterations and impaired systolic and diastolic function. This cohort also showed reduced LV microvascular perfusion, the presence of LGE, and unfavorable VI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Mechanisms of the Accelerated Li+ Conduction in MOF-based Solid-State Polymer Electrolytes for All-Solid-State Lithium Metal Batteries.

Solid polymer electrolytes (SPEs) for lithium metal batteries have garnered considerable interests owing to their low cost, flexibility, lightweight, and favorable interfacial compatibility with battery electrodes. Their soft mechanical nature compared to solid inorganic electrolytes give them a large advantage to be used in low pressure solid-state lithium metal batteries (SSLMBs), which can avoid the cost and weight of the pressure cages. However, the application of SPEs has been hindered by their relatively low ionic conductivity. In addressing this limitation, enormous efforts have been devoted to the experimental investigation and theoretical calculations/simulation of new polymer classes. Recently, metal-organic frameworks (MOFs) have been shown to be effective in enhancing ion transport in SPEs. However, the mechanisms in enhancing Li+ conductivity have rarely been systematically and comprehensively analyzed. Therefore, this review provides an in-depth summary of the mechanisms of MOF-enhanced Li+ transport in MSPEs in terms of polymer, MOF, MOF/polymer interface (MPI) and solid electrolyte interface (SEI) aspects, respectively. Moreover, the understanding of Li+ conduction mechanisms through employing advanced characterization tools, theoretical calculations and simulations are also reviewed in this review. Finally, the main challenges in developing MSPEs are deeply analyzed and the corresponding future research directions are also proposed. This article is protected by copyright. All rights reserved.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophil phagocytic activity and reduced inflammatory cytokine production via activation of the NF-κB pathway. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

A Mendelian randomization investigation of the causal association between the gut microbiota and sleep disorders.

Background: Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the causal associations between specific gut microbiota and sleep disorders. Methods: Data on gut genera were obtained from the MiBioGen consortium. Twenty-four cohorts with 18,340 individuals of European origin were included. Sleep disorder data, which included 216,454 European individuals, were retrieved from the FinnGen Biobank. Subsequently, two-sample Mendelian randomization was performed to analyze associations between sleep disorders and specific components of the gut microbiota. Results: Inverse variance weighting (IVW) revealed a negative correlation between Coprobacter and sleep disorders (OR = 0.797, 95% CI = 0.66-0.96, and p = 0.016), a positive correlation between Lachnospiraceae and sleep disorders (OR = 1.429, 95% CI = 1.03-1.98, and p = 0.032), a negative association between Oscillospira and sleep disorders (OR = 0.745, 95% CI = 0.56-0.98, and p = 0.038), and a negative association between Peptococcus and sleep disorders (OR = 0.858, 95% CI = 0.74-0.99, p = 0.039). Conclusion: A significant causal relationship was found between four specific gut microbiota and sleep disorders. One family, Lachnospiraceae, was observed to increase the risk of sleep disorders, while three genera, namely, Coprobacter, Oscillospira, and Peptococcus, could reduce the risk of sleep disorders. However, further investigations are needed to confirm the specific mechanisms by which the gut microbiota affects sleep.

The rapidly evolving X-linked MIR-506 family fine-tunes spermatogenesis to enhance sperm competition.

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Over-the-scope clip as a rescue treatment for massive bleeding due to Dieulafoy lesion at the colorectal anastomosis: A case report.

RATIONALE: The bleeding of Dieulafoy lesion predominantly involves the proximal stomach and leads to severe gastrointestinal bleeding. However, these lesions have also been reported in the whole gastrointestinal tract. Bleeding of Dieulafoy lesions at the anastomosis was seldomly reported and was very easy to be ignored clinically. PATIENT CONCERNS: We describe a 72-year-old woman with a past history of surgery for rectal carcinoma hospitalized with chief complaint of massive rectal bleeding. No gross bleeding lesion was found during the first emergency colonoscopy. Despite multiple blood transfusions, her hemoglobin rapidly dropped to 5.8 g/dL. DIAGNOSIS: She was diagnosed with Dieulafoy lesion at the colorectal anastomosis during the second emergency colonoscopy. INTERVENTIONS: Primary hemostasis was achieved by endoscopic hemostatic clipping. However, she experienced another large volume hematochezia 3 days later, and then received another endoscopic hemostatic clipping. She was improved and discharged. However, this patient underwent hematochezia again 1 month later. Bleeding was arrested successfully after the over-the-scope clip (OTSC) was placed during the fourth emergency colonoscopy. OUTCOMES: This patient underwent 4 endoscopic examinations and treatments during 2 hospitalizations. The lesion was overlooked during the first emergency colonoscopy. The second and third endoscopes revealed Dieulafoy lesion at the colorectal anastomosis and performed endoscopic hemostatic clippings, but delayed rebleeding occurred. The bleeding was stopped after the fourth emergency colonoscopy using OTSC. There was no further rebleeding during hospitalization and after 2-year of follow-up. LESSONS: As far as we know, there is no reported case of lower gastrointestinal bleeding caused by Dieulafoy lesion at the colorectal anastomosis, OTSC is a safe and effective rescue treatment for Dieulafoy lesions.

Precise Distance Control and Functionality Adjustment of Frustrated Lewis Pairs in Metal-Organic Frameworks.

We report the construction of frustrated Lewis pairs (FLPs) in a metal-organic framework (MOF), where both Lewis acid (LA) and Lewis base (LB) are fixed to the backbone. The anchoring of a tritopic organoboron linker as LA and a monotopic linker as LB to separate metal oxide clusters in a tetrahedron geometry allows for the precise control of distance between them. As the type of monotopic LB linker varies, pyridine, phenol, aniline, and benzyl alcohol, a series of 11 FLPs were constructed to give fixed distances of 7.1, 5.5, 5.4, and 4.8 Å, respectively, revealed by 11B-1H solid-state nuclear magnetic resonance spectroscopy. Keeping LA and LB apart by a fixed distance makes it possible to investigate the electrostatic effect by changing the functional groups in the monotopic LB linker, while the LA counterpart remains unaffected. This approach offers new chemical environments of the active site for FLP-induced catalysis.

Adaptation and validation of the Claremont Purpose Scale to measure Chinese adolescents' purpose in life.

Despite purpose measures being developed for adolescents, quantitative research investigating purposes prior to late adolescence and in non-Western societies remains nascent. This study evaluated the psychometric soundness of the Claremont Purpose Scale among Chinese adolescents. An initial prestudy (n = 34) was conducted to ensure linguistic equivalence. Subsequently, Study 1 (n = 1691) assessed the scale's reliability and factor structure, also investigating its functional equivalence across gender, adolescence stages, and language versions at the item level. Study 2 (n = 7842) investigated the scale's construct, convergent, predictive, and incremental validity, as well as tested for the scale's measurement invariance across different groups at the scale level. The results support the scale's use as a tool for researchers and practitioners to understand and cultivate purpose in adolescents.

Impact of obesity-related indicators on first-pass effect in patients with ischemic stroke receiving mechanical thrombectomy.

PURPOSE: The first-pass effect (FPE), defined as complete revascularization after a single thrombectomy pass in large vessel occlusion, is a predictor of good prognosis in patients with acute ischemic stroke (AIS) receiving mechanical thrombectomy (MT). We aimed to evaluate obesity-related indicators if possible be predictors of FPE. METHODS: We consecutively enrolled patients with AIS who were treated with MT between January 2019 and December 2021 at our institution. Baseline characteristics, procedure-related data, and laboratory test results were retrospectively analyzed. A multivariable logistic regression analysis was performed to evaluate the independent predictors of FPE. RESULTS: A total of 151 patients were included in this study, of whom 47 (31.1%) had FPE. After adjusting for confounding factors, the independent predictors of achieving FPE were low levels of body mass index (BMI) (OR 0.85, 95% CI 0.748 to 0.971), non-intracranial atherosclerotic stenosis (OR 4.038, 95% CI 1.46 to 11.14), and non-internal carotid artery occlusion (OR 13.14, 95% CI 2.394 to 72.11). Patients with lower total cholesterol (TC) (< 3.11 mmol/L) were more likely to develop FPE than those with higher TC (≥ 4.63 mmol/L) (OR 4.280; 95% CI 1.24 to 14.74) CONCLUSION: Lower BMI, non-intracranial atherosclerotic stenosis, non-internal carotid artery occlusion, and lower TC levels were independently associated with increased rates of FPE in patients with AIS who received MT therapy. FPE was correlated with better clinical outcomes after MT.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Comparative analysis of codon usage patterns in the chloroplast genomes of nine forage legumes.

Leguminosae is one of the three largest families of angiosperms after Compositae and Orchidaceae. It is widely distributed and grows in a variety of environments, including plains, mountains, deserts, forests, grasslands, and even waters where almost all legumes can be found. It is one of the most important sources of starch, protein and oil in the food of mankind and also an important source of high-quality forage material for animals, which has important economic significance. In our study, the codon usage patterns and variation sources of the chloroplast genome of nine important forage legumes were systematically analyzed. Meanwhile, we also constructed a phylogenetic tree based on the whole chloroplast genomes and protein coding sequences of these nine forage legumes. Our results showed that the chloroplast genomes of nine forage legumes end with A/T bases, and seven identical high-frequency (HF) codons were detected among the nine forage legumes. ENC-GC3s mapping, PR2 analysis, and neutral analysis showed that the codon bias of nine forage legumes was influenced by many factors, among which natural selection was the main influencing factor. The codon usage frequency showed that the Nicotiana tabacum and Saccharomyces cerevisiae can be considered as receptors for the exogenous expression of chloroplast genes of these nine forage legumes. The phylogenetic relationships of the chloroplast genomes and protein coding genes were highly similar, and the nine forage legumes were divided into three major clades. Among the clades Melilotus officinalis was more closely related to Medicago sativa, and Galega officinalis was more closely related to Galega orientalis. This study provides a scientific basis for the molecular markers research, species identification and phylogenetic studies of forage legumes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01421-0.

Right superior frontal gyrus: A potential neuroimaging biomarker for predicting short-term efficacy in schizophrenia.

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ.

Crystalline metal phosphide-coated amorphous iron oxide-hydroxide (FeOOH) with oxygen vacancies as highly active and stable oxygen evolution catalyst in alkaline seawater at high current density.

In this study, we employed a straightforward phosphorylation approach to achieve a dual objective: constructing c-a heterostructures consisting of crystalline Ni12P5 and amorphous FeOOH, while simultaneously enhancing oxygen vacancies. The resulting oxygen evolution reaction (OER) catalyst, Ni12P5/FeOOH/NF, exhibited remarkable performance with current densities of 500 mA cm-2 in both 1 M KOH and 1 M KOH + seawater, requiring low overpotentials of only 288 and 365 mV, respectively. Furthermore, Ni12P5/FeOOH/NF exhibited only a slight increase in overpotential, with increments of 18 mV and 70 mV in 1 M KOH after 15 and 150 h, and 32 mV and 108 mV in 1 M KOH + seawater at 500 mA cm-2 after 15 and 150 h, respectively. This minimal change can be attributed to the stabilized c-a structure, the protective coating of Ni12P5, and superhydrophilic. Through in-situ Raman and ex-situ XPS analysis, we discovered that Ni12P5/FeOOH/NF can undergo a reconfiguration into an oxygen vacancy-rich (Fe/Ni)OOH phase during OER process. The elevated OER activity is mainly due to the contribution of the oxygen vacancy-rich (Fe/Ni)OOH phase from the reconfigure of the Ni12P5/FeOOH/NF. This finding emphasizes the critical role of oxygen vacancies in facilitating the production of OO species and overcoming the limitations associated with OOH formation, ultimately enhancing the kinetics of the OER.

A new model for dynamic mapping of effective connectivity in task fMRI.

Whole-brain dynamic functional connectivity is a growing area in neuroimaging research, encompassing data-driven methods for investigating how large-scale brain networks dynamically reorganize during resting states. However, this approach has been rarely applied to functional magnetic resonance imaging (fMRI) data acquired during task performance. In this study, we first combined the psychophysiological interactions (PPI) and sliding-window methods to analyze dynamic effective connectivity of fMRI data obtained from subjects performing the N-back task within the Human Connectome Project dataset. We then proposed a hypothetical model called Condition Activated Specific Trajectory (CAST) to represent a series of spatiotemporal synchronous changes in significantly activated connections across time windows, which we refer to as a trajectory. Our finding demonstrate that the CAST model outperforms other models in terms of intra-group consistency of individual spatial pattern of PPI connectivity, overall representational ability of temporal variability and hierarchy for individual task performance and cognitive traits. This dynamic view afforded by the CAST model reflects the intrinsic nature of coherent brain activities.

SLC7A11-ROS/αKG-AMPK axis regulates liver inflammation through mitophagy and impairs liver fibrosis and NASH progression.

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH. Upregulated SLC7A11 level was also detected in two murine NASH models. Functional studies showed that SLC7A11 knockdown or knockout had augmented steatohepatitis with suppression of inflammatory markers in mice. However, overexpression of SLC7A11 dramatically alleviated diet-induced NASH pathogenesis. Mechanically, SLC7A11 decreased reactive oxygen species (ROS) level and promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, SLC7A11 impaired expression of NLRP3 inflammasome components through AMPK-mitophagy axis. IL-1ß release through NLRP3 inflammasome recruited myeloid cells and promoted hepatic stellate cells (HSCs) activation, which contributed to the progression of liver injury and fibrosis. Anti-IL-1ß and anakinra might attenuate the hepatic inflammatory response evoked by SLC7A11 knockdown. Moreover, the upregulation of SLC7A11 in NASH was contributed by lipid overload-induced JNK-c-Jun pathway. In conclusions, SLC7A11 acts as a protective factor in controlling the development of NASH. Upregulation of SLC7A11 is protective by regulating oxidation, αKG and energy metabolism, decreasing inflammation and fibrosis.

A novel membrane-free electrochemical separation-filtering crystallization coupling process for treating circulating cooling water.

The traditional electrochemical descaling process exhibits drawbacks, including low OH- utilization efficiency, constrained cathode deposition area, and protracted homogeneous precipitation time. Consequently, this study introduces a novel membrane-free electrochemical separation-filtering crystallization (MFES-FC) coupling process to treat circulating cooling water (CCW). In the membrane-free electrochemical separation (MFES) system, OH- is rapidly extracted by pump suction from the porous cathode boundary layer solution, preventing neutralization with H+, thereby enhancing the removal of Ca2+ and Mg2+. Experimental results indicate that the pH of the pump suction water can swiftly increase from 8.13 to 11.42 within 10 min. Owing to the high supersaturation of the pump suction water, this study couples the MFES with a filtration crystallization (FC) system that employs activated carbon as the medium. This approach captures scale particles to enhance water quality and expedites the homogeneous precipitation of hardness ions, shortening the treatment time while further augmenting the removal rate. After the MFES-FC treatment, the single-pass removal rates for total hardness, Ca2+ hardness, Mg2+ hardness, and alkalinity in the effluent reached 92 %, 97 %, 64 %, and 67 %, respectively, with turbidity of 3 NTU, current efficiency of 86.6 %, and energy consumption of 7.19 kWh·kg-1 CaCO3. This coupling process facilitates an effective removal of hardness and alkalinity at a comparatively low cost, offering a new reference and inspiration for advancements in electrochemical descaling technology.

DDX20 is required for cell-cycle reentry of prospermatogonia and establishment of spermatogonial stem cell pool during testicular development in mice.

RNA-binding proteins (RBPs), as key regulators of mRNA fate, are abundantly expressed in the testis. However, RBPs associated with human male infertility remain largely unknown. Through bioinformatic analyses, we identified 62 such RBPs, including an evolutionarily conserved RBP, DEAD-box helicase 20 (DDX20). Male germ-cell-specific inactivation of Ddx20 at E15.5 caused T1-propsermatogonia (T1-ProSG) to fail to reenter cell cycle during the first week of testicular development in mice. Consequently, neither the foundational spermatogonial stem cell (SSC) pool nor progenitor spermatogonia were ever formed in the knockout testes. Mechanistically, DDX20 functions to control the translation of its target mRNAs, many of which encode cell-cycle-related regulators, by interacting with key components of the translational machinery in prospermatogonia. Our data demonstrate a previously unreported function of DDX20 as a translational regulator of critical cell-cycle-related genes, which is essential for cell-cycle reentry of T1-ProSG and formation of the SSC pool.

Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Large-scale genomic survey with deep learning-based method reveals strain-level phage specificity determinants.

BACKGROUND: Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversity within phage populations presents a considerable challenge. Currently, there is a notable lack of tools designed for large-scale characterization of phage receptor-binding proteins, which are crucial in determining the phage host range. RESULTS: In this study, we present SpikeHunter, a deep learning method based on the ESM-2 protein language model. With SpikeHunter, we identified 231,965 diverse phage-encoded tailspike proteins, a crucial determinant of phage specificity that targets bacterial polysaccharide receptors, across 787,566 bacterial genomes from 5 virulent, antibiotic-resistant pathogens. Notably, 86.60% (143,200) of these proteins exhibited strong associations with specific bacterial polysaccharides. We discovered that phages with identical tailspike proteins can infect different bacterial species with similar polysaccharide receptors, underscoring the pivotal role of tailspike proteins in determining host range. The specificity is mainly attributed to the protein's C-terminal domain, which strictly correlates with host specificity during domain swapping in tailspike proteins. Importantly, our dataset-driven predictions of phage-host specificity closely match the phage-host pairs observed in real-world phage therapy cases we studied. CONCLUSIONS: Our research provides a rich resource, including both the method and a database derived from a large-scale genomics survey. This substantially enhances understanding of phage specificity determinants at the strain level and offers a valuable framework for guiding phage selection in therapeutic applications.