Transcription-induced active forces suppress chromatin motion.

The organization of interphase chromosomes in a number of species is starting to emerge thanks to advances in a variety of experimental techniques. However, much less is known about the dynamics, especially in the functional states of chromatin. Some experiments have shown that the motility of individual loci in human interphase chromosome decreases during transcription and increases upon inhibiting transcription. This is a counterintuitive finding because it is thought that the active mechanical force (F) on the order of ten piconewtons, generated by RNA polymerase II (RNAPII) that is presumably transmitted to the gene-rich region of the chromatin, would render it more open, thus enhancing the mobility. We developed a minimal active copolymer model for interphase chromosomes to investigate how F affects the dynamical properties of chromatin. The movements of the loci in the gene-rich region are suppressed in an intermediate range of F and are enhanced at small F values, which has also been observed in experiments. In the intermediate F, the bond length between consecutive loci increases, becoming commensurate with the distance at the minimum of the attractive interaction between nonbonded loci. This results in a transient disorder-to-order transition, leading to a decreased mobility during transcription. Strikingly, the F-dependent change in the locus dynamics preserves the organization of the chromosome at [Formula: see text]. Transient ordering of the loci, which is not found in the polymers with random epigenetic profiles, in the gene-rich region might be a plausible mechanism for nucleating a dynamic network involving transcription factors, RNAPII, and chromatin.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.

Cognitive and Hippocampal Changes in Older Adults With Subjective Cognitive Decline After Acupuncture Intervention.

OBJECTIVE: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals. METHODS: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks. RESULTS: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group. CONCLUSION: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level.

Factors affecting nurses' emergency competencies in public health emergency: A cross-sectional study based on the stress-coping adaptation model.

OBJECTIVES: To investigate the factors associated with stress, resilience, coping styles, and emergency competencies when nurses are faced with a public health emergency. DESIGN: This study used a cross-sectional design. SAMPLE: Study data came from a survey of 646 nurses who were from a tertiary hospital in Southern China in March-June 2022. METHODS: Participants responded to self-report questionnaires through a web-based survey. Stress, resilience, emergency competencies, and response to public emergencies were assessed using the Perceived Stress Scale, Connor-Davidson Resilience Scale, the core competencies of nurses in public health emergencies, and a simplified coping style questionnaire. RESULTS: A total of 646 nurses participated in this study. Slightly over half of the participants were ≤30 years old, and almost all were female. Resilience, positive coping, and negative coping were positively correlated with emergency competencies. Multiple linear regression analysis demonstrated that resilience, working years, and participation in the treatment of infectious diseases were significant predictors of emergency competencies. CONCLUSION: The findings suggest that nurses require additional training in emergency management and clinical practice to enhance their emergency competencies. More interventions and social support should be provided to improve nurses' resilience and positive coping strategies when they encounter public health emergencies.

Enabling Highly Robust Full-Color Ultralong Room-Temperature Phosphorescence and Stable White Organic Afterglow from Polycyclic Aromatic Hydrocarbons.

In this work, full-color and stable white organic afterglow materials with outstanding water, organic solvents, and temperature resistances have been developed for the first time by embedding the selected polycyclic aromatic hydrocarbons into melamine-formaldehyde polymer via solution polymerization. The afterglow quantum yields and lifetimes of the resulting polymer films were up to 22.7 % and 4.83 s, respectively, under ambient conditions. For the coronene-doped sample, its afterglow color could be linearly tuned between yellow and blue by adjusting the temperature, and it could still emit an intense blue afterglow with a lifetime of 0.68 s at 440 K. Moreover, the films showed a bright and stable white afterglow at 370 K with a lifetime of 2.80 s and maintained an excellent afterglow performance after soaking in water and organic solvents for more than 150 days. In addition, the application potential of the polymer films in information encryption and anti-counterfeiting was also demonstrated.

Anti-CD79b/CD3 bispecific antibody combined with CAR19-T cells for B-cell lymphoma treatment.

CD19 CAR-T (chimeric antigen receptor-T) cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). Therefore, novel therapeutic strategies are urgently required. In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, BV28-OKT3 redirected CAR19-T cells to CD79b+ CD19- lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b+ CD19- lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR- T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in vitro and in vivo. In addition, BV28-OKT3 elicited the cytotoxicity of donor-derived T cells toward lymphoma cells in vitro, which depended on the presence of tumor cells. Therefore, our findings provide a new clinical treatment strategy for recurrent and refractory B-cell lymphoma by combining CD79b/CD3 BsAb with CAR19-T cells.

Bright Organic Mechanoluminescence and Remarkable Mechanofluorochromism from Circularly Polarized TADF Enantiomers with Aggregation-Induced Emission Properties.

The development of circularly polarized thermally activated delayed fluorescence (CP-TADF) luminogens with stimuli-response characteristics remains challenging. Herein, a pair of organic enantiomers, S-CzTA and R-CzTA, with aggregation-induced emission properties, have been successfully developed by introducing chiral 1,2,3,4-tetrahydronaphthalene and carbazole to phthalimide. They present CP-TADF properties in toluene solutions, giving dissymmetric factors of 0.84×10-3 and -1.03×10-3 , respectively. In the crystalline state, both S-CzTA and R-CzTA can emit intense blue TADF and produce very bright sky-blue mechanoluminescence (ML) and remarkable mechanofluorochromism (MFC) under the stimuli of mechanical force. Single-crystal analysis and theoretical calculation results suggest that their ML activities are probably associated with their chiral and polar molecular structures and unique non-centrosymmetric molecular packing modes. Furthermore, the MFC properties of the enantiomers likely originate from the destruction of crystal structure, leading to the planarization of molecular conformation. This work may provide helpful guidance for developing new CP-TADF materials with force-stimuli-responsive properties.

The Pathological Mechanism of Neuronal Autophagy-Lysosome Dysfunction After Ischemic Stroke.

The abnormal initiation of autophagy flux in neurons after ischemic stroke caused dysfunction of autophagy-lysosome, which not only led to autophagy flux blockage, but also resulted in autophagic death of neurons. However, the pathological mechanism of neuronal autophagy-lysosome dysfunction did not form a unified viewpoint until now. In this review, taking the autophagy lysosomal dysfunction of neurons as a starting point, we summarized the molecular mechanisms that led to neuronal autophagy lysosomal dysfunction after ischemic stroke, which would provide theoretical basis for the clinical treatment of ischemic stroke.

NIR-responsive molybdenum (Mo)-based nanoclusters enhance ROS scavenging for osteoarthritis therapy.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders globally, and treating OA remains a significant challenge. Currently, pharmacological treatments primarily aim to alleviate the OA symptoms associated with inflammation and pain, and no disease-modifying therapies are available to delay OA development and progression. Reactive oxygen species (ROS) play an essential role in OA development and progression, which are a promising target for curing OA. In this study, it was found that photothermal properties of near-infrared (NIR) irradiation enhanced the ROS scavenging activity of molybdenum-based polyoxometalate (POM) nanoclusters. Because of enhanced ROS scavenging, NIR-responsive POM nanoclusters were developed as novel excellent nano-antioxidants for OA protection. The results demonstrated that NIR-responsive POM exhibited outstanding antioxidant activity and superexcellent anti-inflammatory effects, which could effectively alleviate the clinical symptoms of OA mice, diminish inflammatory cytokines, reduce catabolic proteases, and mitigate the progression of OA. Meanwhile, the local treatment had no side effects on normal tissues. Thus, this study pioneered the application of POM for alleviating OA with expected safety and efficiency.

Theory of the center-of-mass diffusion and viscosity of microstructured and variable sequence copolymer liquids.

Biomolecular condensates formed through the phase separation of proteins and nucleic acids are widely observed, offering a fundamental means of organizing intracellular materials in a membrane-less fashion. Traditionally, these condensates have been regarded as homogeneous isotropic liquids. However, in analogy with some synthetic copolymer systems, our recent theoretical research has demonstrated that model biomolecular condensates can exhibit a microemulsion-like internal structure, contingent upon the specific sequence, inter-chain site-site interactions, and concentrated phase polymer density. Motivated by these considerations, here we present a microscopic dynamical theory for the self-diffusion constant and viscosity of a simpler class of model systems - concentrated unentangled A/B regular multiblock copolymer solutions. Our approach integrates static equilibrium local and microdomain scale structural information obtained from PRISM integral equation theory and the time evolution of the autocorrelation function of monomer scale forces at the center-of-mass level to determine the polymer diffusion constant and viscosity in a weak caging regime far from a glass or gel transition. We focus on regular multi-block systems both for simplicity and for its relevance to synthetic macromolecular science. The impact of sequence and inter-chain attraction strength on the slowing down of copolymer mass transport and flow due to local clustering enhanced collisional friction and emergent microdomain scale ordering are established. Analytic analysis and metrics employed in the study of biomolecular condensates are employed to identify key order parameters that quantity how attractive forces, packing structure, multiblock sequence, and copolymer density determine dynamical slowing down above and below the crossover to a fluctuating polymeric microemulsion state.

Different photoprotective strategies for white leaves between two co-occurring Actinidia species.

At the outer canopy, the white leaves of Actinidia kolomikta can turn pink but they stay white in A. polygama. We hypothesized that the different leaf colors in the two Actinidia species may represent different photoprotection strategies. To test the hypothesis, leaf optical spectra, anatomy, chlorophyll a fluorescence, superoxide (O2 ˙- ) concentration, photosystem II photo-susceptibility, and expression of anthocyanin-related genes were investigated. On the adaxial side, light reflectance was the highest for white leaves of A. kolomikta, followed by its pink leaves and white leaves of A. polygama, and the absorptance for white leaves of A. kolomikta was the lowest. Chlorophyll and carotenoid content of white and pink leaves in A. kolomikta were significantly lower than those of A. polygama, while the relative anthocyanin content of pink leaves was the highest. Chloroplasts of palisade cells of white leaves in A. kolomikta were not well developed with a lower maximum quantum efficiency of PSII than the other types of leaves (pink leaves of A. kolomikta and white leaves of A. Polygama at the inner/outer canopy). After high light treatment from the abaxial surface, Fv /Fm decreased to a larger extent for white leaves of A. kolomikta than pink leaf and white leaves of A. polygama, and its non-photochemical quenching was also the lowest. White leaves of A. kolomikta showed higher O2 ˙- concentration compared to pink leaves under the same strong irradiance. The expression levels of anthocyanin biosynthetic genes in pink leaves were higher than in white leaves. These results indicate that white leaves of A. kolomikta apply a reflection strategy for photoprotection, while pink leaves resist photoinhibition via anthocyanin accumulation.

Elevated NT-proBNP predicts unfavorable outcomes in patients with acute ischemic stroke after thrombolytic therapy.

OBJECTIVE: Few studies correlated n-terminal pro-brain natriuretic peptide (NT-proBNP) with early neurological deterioration (END) and prognosis of acute ischaemic stroke (AIS) patients with rt-PA intravenous thrombolysis. Therefore this study aimed to investigate the relationship between NT-proBNP and END, and prognosis after intravenous thrombolysis in patients with AIS. METHODS: A total of 325 patients with AIS were enrolled. We performed the natural logarithm transformation on the NT-proBNP [ln(NT-proBNP)]. Univariate and multivariate logistic regression analyses were performed to assess the relationship between ln(NT-proBNP) and END, and prognosis and receiver operating characteristic (ROC) curves were used to show the sensitivity and specificity of NT-proBNP. RESULTS: After thrombolysis, among 325 patients with AIS, 43 patients (13.2%) developed END. In addition, three months follow-up showed a poor prognosis in 98 cases (30.2%) and a good prognosis in 227 cases (69.8%). Multivariate logistic regression analysis showed that ln(NT-proBNP) was an independent risk factor for END (OR = 1.450,95%CI:1.072 ~ 1.963, P = 0.016) and poor prognosis at three months follow-up (OR = 1.767, 95%CI: 1.347 ~ 2.317, P < 0.001) respectively. According to ROC curve analysis, ln(NT-proBNP) (AUC 0.735, 95%CI: 0.674 ~0.796, P < 0.001) had a good predictive value for poor prognosis, with a predictive value of 5.12 and sensitivity and specificity of 79.59% and 60.35% respectively. When combined with NIHSS to predict END(AUC 0.718, 95%CI: 0.631 ~ 0.805, P < 0.001) and poor prognosis(AUC 0.780, 95%CI: 0.724 ~ 0.836, P < 0.001), the predictive value of the model is further improved. CONCLUSION: NT-proBNP is independently associated with END and poor prognosis in patients with AIS following intravenous thrombolysis and has a particular predictive value for END and poor prognosis.

Liquid state theory study of the phase behavior and macromolecular scale structure of model biomolecular condensates.

Biomolecular condensates can form through the liquid-liquid phase separation (LLPS) of proteins and RNAs in cells. However, other states of organization, including mesostructured network microstructures and physical gels, have been observed, the physical mechanism of which are not well understood. We use the Polymer Reference Interaction Site Model liquid state integral equation theory to study the equilibrium behavior of (generally aperiodic in sequence) biomolecular condensates based on a minimal sticker-spacer associating polymer model. The role of polymer packing fraction, sequence, and the strength and range of intermolecular interactions on macromolecular scale spatial organization and phase behavior is studied for typical sticker-spacer sequences. In addition to the prediction of conventional LLPS, a sequence-dependent strongly fluctuating polymeric microemulsion homogeneous state is predicted at high enough concentrations beyond the so-called Lifshitz-like point, which we suggest can be relevant to the dense phase of microstructured biomolecular condensates. New connections between local clustering and the formation of mesoscopic microdomains, the influence of attraction range, compressibility, and the role of spatial correlations across scales, are established. Our results are also germane to understanding the polymer physics of dense solutions of nonperiodic and unique sequence synthetic copolymers and provide a foundation to create new theories for how polymer diffusion and viscosity are modified in globally isotropic and homogeneous dense polymeric microemulsions.

Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone-treated rats.

Oxycodone is a highly prescribed opioid and its abuse has been rampant. Accumulating evidence shows that the cannabinoid CB1 receptor (CB1R) plays a key role in mediating rewarding effects to opioids. However, the downstream signalling of CB1R induced by oxycodone remains unclear. The neuropeptide oxytocin is well known as a potential remedy for drug addiction. Thus, our study aims to explore the mechanism of oxycodone-induced learning and memory deficits underlying the endocannabinoid system (ECS) and the effect of oxytocin. Rats were intraperitoneally injected with oxycodone once a day for eight consecutive day. Novel object recognition, resident-intruder and Morris Water Maze tests were employed to assess the cognitive, social and spatial memory of the rats after oxycodone withdrawal. The (co-)expression of CB1R, cyclin-dependent kinase 5 (Cdk5), regulatory protein p25, tau and phosphorylated tau was measured 1 day after the last behavioural test. The histopathological staining and synaptic density in the hippocampus were observed as well. We found that oxycodone upregulated the expression of p-GSK3ß, co-expression of p-Cdk5 and p25 through CB1R. This finding was accompanied by elevation of pSer396, pSer404 in the tau, and reduction of the number of neurons, dendritic spines and synaptic density in the hippocampus. Furthermore, i.c.v. treatment with oxytocin ameliorates memory deficits in oxycodone-treated rats through inhibition of the ECS. We propose further studies on the clinical use of this neuropeptide, which may potentially cure drug addiction.

The characteristics of the urogenital fascia in the retrorectal space based on male cadaveric dissection and its clinical application.

BACKGROUND: The architecture of retrorectal fasciae is complex, as determined by different anatomical concepts. The aim of this study was to examine the anatomical characteristics of the inferomedial extension of the urogenital fascia (UGF) involving the pelvis to explore its relationship with the adjacent fasciae. Furthermore, we have expounded on the clinical application of UGF. METHOD: For our study, we examined 20 adult male pelvic specimens fixed in formalin, including 2 entire pelvic specimens and 18 semipelvic specimens. Our department has performed 466 laparoscopic rectal cancer procedures since January 2020. We reviewed the surgical videos involving UGF preservation and analyzed the anatomy of the UGF. RESULTS: The bilateral hypogastric nerves ran between the visceral and parietal layers of the UGF. The visceral fascia migrated ventrally at the fourth sacral vertebra, which formed the rectosacral fascia together with the fascia propria of the rectum; the parietal layer continually extended to the pelvic diaphragm, terminating at the levator ani muscle. At the third to fourth sacral vertebra level, the two layers constituted the lateral ligaments. CONCLUSION: The double layers of the UGF are vital structures for comprehending the posterior fascia relationship of the rectum. The upper segment between the fascia propria of the rectum and the visceral layer has no evident nerves or blood vessels and is regarded as the " holy plane" for the operation.

Switchable and Highly Robust Ultralong Room-Temperature Phosphorescence from Polymer-Based Transparent Films with Three-Dimensional Covalent Networks for Erasable Light Printing.

In this work, an efficient polymer-based organic afterglow system, which shows reversible photochromism, switchable ultralong organic phosphorescence (UOP), and prominent water and chemical resistance simultaneously, has been developed for the first time. By doping phenoxazine (PXZ) and 10-ethyl-10H-phenoxazine (PXZEt) into epoxy polymers, the resulting PXZ@EP-0.25 % and PXZEt@EP-0.25 % films show unique photoactivated UOP properties, with phosphorescence quantum yields and lifetimes up to 10.8 % and 845 ms, respectively. It is found that the steady-state luminescence and UOP of PXZ@EP-0.25 % are switchable by light irradiation and thermal annealing. Moreover, the doped films can still produce conspicuous UOP after soaking in water, strong acid and base, and organic solvents for more than two weeks, exhibiting outstanding water and chemical resistance. Inspired by these exciting results, the PXZ@EP-0.25 % has been successfully exploited as an erasable transparent film for light printing.

Color-Tunable Dual-Mode Organic Afterglow from Classical Aggregation-Caused Quenching Compounds for White-Light-Manipulated Anti-Counterfeiting.

Color-tunable dual-mode organic afterglow excited by ultraviolet (UV) and white light was achieved from classical aggregation-caused quenching compounds for the first time. Specifically, two luminescent systems, which could produce significant organic afterglow composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence under ambient conditions, were constructed by doping fluorescein sodium and calcein sodium into aluminum sulfate. Their lifetimes surpassed 600 ms, and the dopant concentrations were as low as 5×10-6  wt %. Moreover, the persistent luminescence colors of the materials could be tuned from blue to green and then to yellow by simply varying the concentrations of guest compounds or the temperature in the range of 260-340 K. Inspired by these exciting results, the afterglow materials were used for UV- and white-light-manipulated anti-counterfeiting and preparation of elastomers with different colors of persistent luminescence.

Chromatin dynamics controls epigenetic domain formation.

In multicellular organisms, nucleosomes carry epigenetic information that defines distinct patterns of gene expression, which are inherited over multiple generations. The enhanced capacity for information storage arises by nucleosome modifications, which are triggered by enzymes. Modified nucleosomes can transfer the mark to others that are in proximity by a positive-feedback (modification begets modification) mechanism. We created a generic polymer model, referred to as 3DSpreader, in which each bead, representing a nucleosome, stochastically switches between unmodified (U) and modified (M) states depending on the states of the neighbors. Modification begins at a specific nucleation site (NS) that is permanently in the M state, and could spread to other loci that is dictated by chromatin dynamics. Transfer of marks among the non-nucleation loci occurs stochastically as chromatin evolves in time. If the spreading rate is slower than the chromatin relaxation rate, which is biologically pertinent, then finite-sized domains form, driven by contacts between nucleosomes through a three-dimensional looping mechanism. Surprisingly, simulations based on the 3DSpreader model result in finite bounded domains that arise without the need for any boundary elements. Maintenance of spatially and temporally stable domains requires the presence of the NS, whose removal eliminates finite-sized modified domains. The theoretical predictions are in excellent agreement with experimental data for H3K9me3 spreading in mouse embryonic stem cells.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

Liraglutide Ameliorates Cerebral Ischemia in Mice via Antipyroptotic Pathways.

It was recently shown that pyroptosis, an inflammatory form of programmed cell death, is critically involved in the pathogenesis of ischemic stroke. Liraglutide (Lg) is a novel long-acting analog of glucagon-like peptide-1 that has potential protective effects against stroke. However, the relationship between Lg and pyroptosis in the brain is not well defined. In this study, we found that injection of Lg significantly improved the recovery of motor function, increased cerebral blood flow and ameliorated cerebral damage in a mouse model of focal cerebral cortical ischemia. Our results revealed that Lg treatment significantly reduced the levels of NLRP3, Caspase1, IL-1ß and the pore-forming protein gasdermin D in microglial cells in vitro, suggesting that the neuroprotective effect of Lg may be achieved through the inhibition of pyroptosis. Furthermore, by using a specific inhibitor of NOD-like receptor protein 3 (NLRP3), we confirmed that the antipyroptotic mechanism of Lg may be mediated by NLRP3 in vivo. Our present study unveils a novel neuroprotective mechanism through which Lg alleviates ischemia by exerting NLRP3-dependent antipyroptotic effects.