AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: An exploratory study.

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

Photoluminescent Properties and Mechanism of Novel Cyanine-Borondifluoride Curcuminoid Hybrids as Red-to-Near Infrared and Endoplasmic Reticulum-Targeting Dyes.

Synthesis-oriented design led us to the discovery of a series of novel cyanine-borondifluoride curcuminoid hybrids called Nanchang Red (NCR) dyes that overcome the intrinsic low synthetic yields of symmetrical cyanine-difluoroboronate (BF2 )-hybridized NIR dyes. The hybridization endows NCR dyes with high molar extinction coefficients, efficient red-to-NIR emission, and enlarged Stokes shifts. Quantum chemical calculations revealed that the asymmetrical layout of the three key electron-withdrawing and electron-donating fragments results in a special pattern of partial charge separation and inconsistent degrees of charge delocalization on their π-conjugated backbones. While the nature of the hemicyanine fragment exerts significant influence on the excitation modes of NCR dyes, the borondifluoride hemicurcuminoid fragment is the major contributor to the enlarged Stokes shifts. Cell imaging experiments illustrated that a subtle change in the N-heterocycle of the hemicyanine fragment has a remarkable effect on the subcellular localization of NCR dyes. Unlike other previously reported cyanine-BF2 hybridized dyes, which mainly target mitochondria, the benzothiazole and indole-based NCR dyes accumulate in both the endoplasmic reticulum (ER) and lipid droplets of HeLa cells, whereas the benzoxazole and quinoline-based NCR dyes stain the ER specifically.

Hepatocytic ballooning in non-alcoholic steatohepatitis: Dilemmas and future directions.

Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in 'real life' situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.

Prognostic impact of deep learning-based quantification in clinical stage 0-I lung adenocarcinoma.

OBJECTIVES: To evaluate the performance of automatic deep learning (DL) algorithm for size, mass, and volume measurements in predicting prognosis of lung adenocarcinoma (LUAD) and compared with manual measurements. METHODS: A total of 542 patients with clinical stage 0-I peripheral LUAD and with preoperative CT data of 1-mm slice thickness were included. Maximal solid size on axial image (MSSA) was evaluated by two chest radiologists. MSSA, volume of solid component (SV), and mass of solid component (SM) were evaluated by DL. Consolidation-to-tumor ratios (CTRs) were calculated. For ground glass nodules (GGNs), solid parts were extracted with different density level thresholds. The prognosis prediction efficacy of DL was compared with that of manual measurements. Multivariate Cox proportional hazards model was used to find independent risk factors. RESULTS: The prognosis prediction efficacy of T-staging (TS) measured by radiologists was inferior to that of DL. For GGNs, MSSA-based CTR measured by radiologists (RMSSA%) could not stratify RFS and OS risk, whereas measured by DL using 0HU (2D-AIMSSA0HU%) could by using different cutoffs. SM and SV measured by DL using 0 HU (AISM0HU% and AISV0HU%) could effectively stratify the survival risk regardless of different cutoffs and were superior to 2D-AIMSSA0HU%. AISM0HU% and AISV0HU% were independent risk factors. CONCLUSION: DL algorithm can replace human for more accurate T-staging of LUAD. For GGNs, 2D-AIMSSA0HU% could predict prognosis rather than RMSSA%. The prediction efficacy of AISM0HU% and AISV0HU% was more accurate than of 2D-AIMSSA0HU% and both were independent risk factors. CLINICAL RELEVANCE STATEMENT: Deep learning algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma. KEY POINTS: • Deep learning (DL) algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma (LUAD). • For GGNs, maximal solid size on axial image (MSSA)-based consolidation-to-tumor ratio (CTR) measured by DL using 0 HU could stratify survival risk than that measured by radiologists. • The prediction efficacy of mass- and volume-based CTRs measured by DL using 0 HU was more accurate than of MSSA-based CTR and both were independent risk factors.

Assessment of Bacillus subtilis fermented Caulerpa microphysa byproduct as feed additive on the growth performance, immune regulation and disease resistance of white shrimp (Litopenaeus vannamei).

In this study, the immunomodulatory and antioxidant activity of fermented Caulerpa microphysa byproduct (FCMB) by Bacillus subtilis was evaluated, and its potential as a feed additive for white shrimp (Litopenaeus vannamei) was explored. In vitro experiments showed that the FCMB supernatant contained polysaccharides, polyphenols and flavonoids, and exhibited antioxidant properties as assessed by various antioxidant assays. Additionally, the FCMB supernatant was found to increase the production rate of reactive oxygen species and the activity of phenoloxidase in hemocytes in vitro. Furthermore, the results of the in vivo feeding trial showed that dietary 5 g kg-1 FCMB significantly improved the weight gain and specific growth rate of white shrimp after 56 days of feeding. Although there were no significant differences in total hemocyte count, phagocytosis, superoxide anion production rate, and phenoloxidase activity among the experimental groups, upregulation of immune-related genes was observed, particularly in the hepatopancreas and hemocytes of shrimps fed with 5 g or 50 g FCMB per kg feed, respectively. In the pathogen challenge assay, white shrimp fed with 5 % FCMB exhibited a higher survival rate compared to the control group following Vibrio parahaemolyticus challenge. Therefore, it is concluded that the fermented byproduct of C. microphysa, FCMB, holds potential as a feed additive for enhancing the growth performance and disease resistance against V. parahaemolyticus in white shrimp.

Nonaqueous Rechargeable Aluminum Batteries: Progresses, Challenges, and Perspectives.

For significantly increasing the energy densities to satisfy the growing demands, new battery materials and electrochemical chemistry beyond conventional rocking-chair based Li-ion batteries should be developed urgently. Rechargeable aluminum batteries (RABs) with the features of low cost, high safety, easy fabrication, environmental friendliness, and long cycling life have gained increasing attention. Although there are pronounced advantages of utilizing earth-abundant Al metals as negative electrodes for high energy density, such RAB technologies are still in the preliminary stage and considerable efforts will be made to further promote the fundamental and practical issues. For providing a full scope in this review, we summarize the development history of Al batteries and analyze the thermodynamics and electrode kinetics of nonaqueous RABs. The progresses on the cutting-edge of the nonaqueous RABs as well as the advanced characterizations and simulation technologies for understanding the mechanism are discussed. Furthermore, major challenges of the critical battery components and the corresponding feasible strategies toward addressing these issues are proposed, aiming to guide for promoting electrochemical performance (high voltage, high capacity, large rate capability, and long cycling life) and safety of RABs. Finally, the perspectives for the possible future efforts in this field are analyzed to thrust the progresses of the state-of-the-art RABs, with expectation of bridging the gap between laboratory exploration and practical applications.

Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

Birth environment interventions and outcomes: A scoping review.

BACKGROUND: The physical environments in which women give birth can contribute positively to meeting both physiologic and psychosocial needs during labor. Most studies on the labor and delivery processes have focused on mitigating pain and providing psychological support. Fewer have explored the influence of the physical birth environment. In this study, we performed a scoping review to compile and examine qualitative and quantitative studies related to the characteristics of physical birth environments and their effects on labor outcomes. METHODS: We searched the PubMed, CINHAL, Cochrane, Web of Science, and MEDLINE databases from inception to May 2022. A total of 13 studies met the criteria for inclusion in our review. Two reviewers screened the titles and full-text articles and extracted data from the included studies. We used summary statistics and narrative summaries to describe the study characteristics, intervention implementation guidelines, intervention selection and tailoring rationale, and intervention effects. RESULTS: In previous research, several elements of birth environments have been shown to provide physical and psychological support to birthing people and to improve outcomes related to the experience of care and pain management. We identified five main themes in the included studies: (1) "hominess;" (2) whether spaces are comfortable for activity; (3) demedicalization of the birth environment; (4) accommodations for birth partners; and (5) providing women with a sense of control over their birth environment. CONCLUSIONS: Birth environments should be designed to promote positive birthing experiences, both physiologically and psychologically. Facilities and those who manage them can improve the experiences and outcomes of service users by modifying or designing spaces that are "homey," comfortable for activity, demedicalized, and include natural elements. In addition, policies that allow the birthing person to control her own environment are key to promoting positive outcomes and satisfaction with the birth experience.

Recent advances in small-molecule fluorescent probes for studying ferroptosis.

Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death driven by excessive lipid peroxidation (LPO). Mounting evidence suggests that the unique modality of cell death is involved in the development and progression of several diseases including cancer, cardiovascular diseases (CVDs), neurodegenerative disorders, etc. However, the pathogenesis and signalling pathways of ferroptosis are not fully understood, possibly due to the lack of robust tools for the highly selective and sensitive imaging of ferroptosis analytes in complex living systems. Up to now, various small-molecule fluorescent probes have been applied as promising chemosensors for studying ferroptosis through tracking the biomolecules or microenvironment-related parameters in vitro and in vivo. In this review, we comprehensively reviewed the recent development of small-molecule fluorescent probes for studying ferroptosis, with a focus on the analytes, design strategies and bioimaging applications. We also provided new insights to overcome the major challenges in this emerging field.

Multiple Nucleocapsid Structural Forms of Shrimp White Spot Syndrome Virus Suggests a Novel Viral Morphogenetic Pathway.

White spot syndrome virus (WSSV) is a very large dsDNA virus. The accepted shape of the WSSV virion has been as ellipsoidal, with a tail-like extension. However, due to the scarcity of reliable references, the pathogenesis and morphogenesis of WSSV are not well understood. Here, we used transmission electron microscopy (TEM) and cryogenic electron microscopy (Cryo-EM) to address some knowledge gaps. We concluded that mature WSSV virions with a stout oval-like shape do not have tail-like extensions. Furthermore, there were two distinct ends in WSSV nucleocapsids: a portal cap and a closed base. A C14 symmetric structure of the WSSV nucleocapsid was also proposed, according to our Cryo-EM map. Immunoelectron microscopy (IEM) revealed that VP664 proteins, the main components of the 14 assembly units, form a ring-like architecture. Moreover, WSSV nucleocapsids were also observed to undergo unique helical dissociation. Based on these new results, we propose a novel morphogenetic pathway of WSSV.

Multifunctional Fluorescent Probe for Simultaneously Detecting Microviscosity, Micropolarity, and Carboxylesterases and Its Application in Bioimaging.

Based on OR logic gate, we proposed a smart near-infrared (NIR) fluorescent probe, named VPCPP, for simultaneously monitoring local microviscosity, micropolarity, and carboxylesterases (CEs) in living cells through blue and red channels. This proposed probe was capable of distinguishing cancer cells from normal cells and had good potential for identifying living liver cell lines. Furthermore, the fluctuations of the three analytes of interest in different cell status was successfully explored. Particularly, facilitated with high-content analysis (HCA) and VPCPP, a simple and efficient high-throughput screening (HTS) platform was first constructed for screening antitumor drugs and studying their effect on the analytes. For the first time, we found that sorafenib-induced ferroptosis led to an increase in the microviscosity and up-regulation of CEs at the same time. Additionally, the procedure that aristolochic acid (AA) induced the overexpression of CEs was verified. Besides, VPCPP was utilized for imaging the variations of the two microenvironment parameters and CEs in the inflammation model. Finally, VPCPP was able to image the tumor ex vivo and in vivo through two channels and one channel separately, as well as to visualize the kidneys and liver ex vivo with dual emissions, which indicated that the probe had great potential for imaging applications such as medical diagnosis, preclinical research, and imaging-guided surgery.

Metabolic dysfunction-associated fatty liver disease and implications for cardiovascular risk and disease prevention.

The newly proposed term "metabolic dysfunction-associated fatty liver disease" (MAFLD) is replacing the old term "non-alcoholic fatty liver disease" (NAFLD) in many global regions, because it better reflects the pathophysiology and cardiometabolic implications of this common liver disease. The proposed change in terminology from NAFLD to MAFLD is not simply a single-letter change in an acronym, since MAFLD is defined by a set of specific and positive diagnostic criteria. In particular, the MAFLD definition specifically incorporates within the classification recognized cardiovascular risk factors. Although convincing evidence supports a significant association between both NAFLD and MAFLD, with increased risk of CVD morbidity and mortality, neither NAFLD nor MAFLD have received sufficient attention from the Cardiology community. In fact, there is a paucity of scientific guidelines focusing on this common and burdensome liver disease from cardiovascular professional societies. This Perspective article discusses the rationale and clinical relevance for Cardiologists of the newly proposed MAFLD definition.

Effects of an art-based intervention in older adults with mild cognitive impairment: a randomised controlled trial.

BACKGROUND: Art-based interventions may delay cognitive decline and improve health-related outcomes in older adults with mild cognitive impairment (MCI). OBJECTIVE: To examine the effects of the Creative Expressive Arts-based Storytelling (CrEAS) program compared to active and waitlist controls on neurocognitive and other health-related outcomes in older people with MCI. DESIGN: Three-arm parallel-group, randomised controlled design. PARTICIPANTS: One-hundred and thirty-five adults with MCI (mean age: 70.93 ± 6.91 years). METHODS: Participants were randomly assigned to intervention (CrEAS, n = 45), active control (n = 45) or waitlist control (n = 45) groups. Interventions were applied once per week for 24 weeks. The primary outcome was global cognitive function; secondary outcomes were specific cognition domains (memory, executive function, language and attention) and other health-related outcomes (anxiety, depression and quality of life [QoL]). All variables were measured at baseline (T0), 24-week follow-up (T1) and 48-week follow-up (T2). RESULTS: Participants in the CrEAS group showed significantly higher global cognitive function (adjusted mean difference [MD] = -0.905, 95% confidence interval [CI] -1.748 to -0.062; P = 0.038) and QoL (adjusted MD = -4.150, 95% CI -6.447 to -1.853; P = 0.001) and lower depression symptoms (adjusted MD = 2.902, 95% CI 0.699-5.104; P = 0.011) post-intervention at the 24-week follow-up compared with the active control group. At 48-week follow-up, only the Auditory Verbal Learning Test Immediate recall score was significantly improved compared with the active control group (adjusted MD = -2.941, 95% CI -5.262 to -0.620; P = 0.014). CONCLUSIONS: Older adults with MCI who participated in the CrEAS program improved their neuropsychological outcomes and QoL and reduced their rate of cognitive deterioration.

Accuracy of non-invasive methods for assessing the progress of labor in the first stage: a systematic review and meta-analysis.

BACKGROUND: The World Health Organization in recent years has emphasized reducing the possibility of unnecessary interventions in natural childbirth, but little is known about the accuracy of non-invasive methods when assessing the progress of labor. This paper presents a literature review to assess strategies that support non-invasive methods for labor during the first stage. It evaluates the available evidence to provide the most suitable assessments and predictions that objectively identify the progress of low-risk labor during the first stage of labor. METHODS: A search for relevant literature was conducted using the electronic databases of PubMed, CINAHL, Web of Sciences, the Cochrane Library, Scopus, Medline (OVID), and CEPS, with publications up to November 2021. Records were screened against pre-specified inclusion/exclusion criteria and the potential papers from Google Scholar were examined to identify additional papers that may have been missed. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to appraise the methodological quality of the included studies. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Two independent investigators extracted the review's characteristics, and discrepancies were resolved by consensus. This review calculated individual and pooled sensitivity, specificity, and positive predictive values, which were exported to STATA (version 14; Stata Corp., College Station, TX) to represent the performance of diagnostic testing. RESULTS: Our search returned 2283 reports of which 13 fulfilled the inclusion criteria, accounting for 2594 women. The subjects were divided into groups according to the diagnostic tests used to assess the progress of their labor, including appearance assessment and sonographic imaging parameters (head perineum distance, HPD; angle of progression, AOP, and other parameters). HPD pooled sensitivity was 0.74 (0.65-0.82), and specificity was 0.77 (0.69-0.84). The pooled diagnostic odds ratio (DOR) was 8.21 (4.67-14.41) and 10.34 (5.02-21.27), respectively. The results of subgroup analysis showed that the summary sensitivity and specificity were of medium accuracy overall. The quality of evidence as assessed with GRADE was low. CONCLUSION: Vaginal examination is an intrinsic element in the use of the partogram, while transperineal ultrasound can also be used as an auxiliary tool. However, the presence of publication bias within the parameters of ultrasound indicates that the diagnostic performance may be overestimated. Thus, randomized controlled trials or large-scale prospective cohort studies are necessary.

TM4SF1 promotes glioma malignancy through multiple mechanisms.

Transmembrane-4 L Six Family member 1 (TM4SF1) belongs to a family of integral membrane proteins implicated in cell growth and tumor progression. Glioma is the most common and aggressive malignant brain tumor in adults. In this study, we showed that TM4SF1 was highly expressed in glioma tumor tissues and cell lines. The expression levels of TM4SF1 were negatively correlated with patients' survival rates. Silencing TM4SF1 by RNA interference inhibited the proliferation, migration, and invasion of glioma cells. Moreover, TM4SF1 silencing induced glioma cell cycle arrest and early apoptosis. In contrast, overexpression of TM4SF1 in glioma cells exhibited the opposite effects. Mechanistically, we found that loss of TM4SF1 reduced phospho-ATK, Cyclin D1, Bcl-2, and MMP-9 levels in glioma cells. Taken together, these findings provide novel insights into glioma pathogenesis and suggest that TM4SF1 may represent a novel target for glioma intervention.

Decellularized matrix could affect the proliferation and differentiation of periodontal ligament stem cells in vitro.

OBJECTIVE AND BACKGROUND: Recently, decellularized matrix (DCM) is considered as a new biomaterial for tissue regeneration. To explore the possible application of DCM in periodontal regeneration, the effect of DCM from three different cells on the proliferation and differentiation of human periodontal ligament stem cells (PDLSCs) was investigated. METHODS: DCM derived from human periodontal ligament cells (PDLCs), dental pulp cells (DPCs), and gingival fibroblasts (GFs) were fabricated using Triton X-100/NH4 OH combined with DNase I. Allogeneic PDLSCs were cultured on PDLC-DCM, DPC-DCM, and GF-DCM, respectively. The proliferative capacity of PDLSCs was evaluated by PicoGreen assay kit. The expression of alkaline phosphatase (ALP), runt-related transcription factor-2 (RUNX2), osteocalcin (OCN), collagen I (COL1), periostin (POSTN), and cementum protein 1 (CEMP1) were detected by qRT-PCR and western blotting. RESULTS: PDLC-DCM, DPC-DCM, and GF-DCM had similar and integrated networks of extracellular matrix, as well as significantly decreased DNA content. Compared with control group in which PDLSCs were directly seeded in culture plates, PDLC-DCM, DPC-DCM, and GF-DCM promoted the proliferation of re-seeded PDLSCs. Additionally, PDLSCs on DCM exhibited higher mRNA and protein expression levels of ALP, RUNX2, OCN, and COL1. The expression of POSTN in PDLC-DCM group was significantly higher than control group at both mRNA and protein levels. CONCLUSIONS: PDLC-DCM, DPC-DCM, and GF-DCM could enhance the proliferation of PDLSCs. PDLC-DCM facilitated osteogenic differentiation and periodontal ligament differentiation of PDLSCs, while DPC-DCM and GF-DCM promoted osteogenic differentiation.

Cohort study on the prognosis of acute cerebral infarction in different circulatory systems at 1-year follow-up.

BACKGROUND: To evaluate the prognosis of acute cerebral infarction at 1-year follow-up in different circulation infarctions. METHODS: Clinical data of 858 consecutive patients with acute cerebral infarction were collected. Of the 858 cases, 21 (2.45%) were lost to follow-up and 837 completed follow-up and thus were enrolled in this study. At 1-year follow-up, death or moderate-to-severe dysfunction (modified Rankin Scale (mRS) ≥ 3 points) was regarded as the poor prognostic endpoint. Univariate analysis and multivariate logistic stepwise regression analysis were performed to assess the prognosis. The prediction probability of indicators was obtained for the multivariate model, and the receiver operating characteristic curve was delineated to calculate the area under the curve (AUC) to predict the fitness of the model. RESULTS: The older the age, the greater the probability of a poor prognosis. Patients with previous diabetes and cerebral infarction had a poor prognosis. The higher the National Institutes of Health Stroke Scale and mRS scores and the lower the Barthel index at admission, the worse the prognosis of the patients. The longer the hospital stay, the worse the prognosis of the patients. The prognosis of different circulation infarctions was different. The AUC of the multivariate model was AUC = 0.893, and the 95% confidence interval was 0.870-0.913, indicating a good fit. The prognosis of anterior circulation infarction (ACI) was worse than that of posterior circulation infarction (PCI) (P < 0.05). The prognosis of patients with ACI and PCI was not significantly different from that of patients with ACI or PCI alone (P > 0.05). CONCLUSIONS: Diabetes, the Barthel index at admission and previous cerebral infarction are poor prognostic factors of acute cerebral infarction. The prognosis of ACI is worse than that of PCI. Different factors affect the prognosis of different circulatory system infarctions.

Multifunctional carbonized nanogels to treat lethal acute hepatopancreatic necrosis disease.

BACKGROUND: Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus (V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse. METHODS: Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 â„ƒ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules. RESULTS: DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed. CONCLUSION: Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.

ARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification.

During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3'-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2-FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development.