Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has ...been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.
Scope
Gut dysbiosis and dysregulation of the gut‐brain‐axis contributes to the pathogenesis of hypertension. Vitamin C (VC) is a common dietary supplement that shows the ability to lower the elevated ...blood pressure in hypertensive animals. Thus, the hypothesis that the gut microbiota is involved in the anti‐hypertensive effect of VC is proposed.
Methods and Results
The changes of the gut microbiota and pathology in a spontaneously hypertensive rat (SHR) model after daily oral intake of VC in dosage of 200 or 1000 mg kg−1 are examined. After 4 weeks, the elevated blood pressure of SHRs in both VC‐treated groups is attenuated. Sequencing of the gut microbiota shows improvement in its diversity and abundance. Bioinformatic analysis suggests restored metabolism and biosynthesis‐related functions of the gut, which are confirmed by the improvement of gut pathology and integrity. Analysis of the hypothalamus paraventricular nucleus (PVN), the central pivot of blood pressure regulation, also shows reduced inflammatory responses and oxidative stress.
Conclusions
The reduced blood pressure, enriched gut microbiota, improved gut pathology and integrity, and reduced inflammatory responses and oxidative stress in the PVN together suggest that the anti‐hypertensive effects of VC involve reshaping of gut microbiota composition and function.
Daily vitamin C (VC) oral intake for 4 weeks reduces the blood pressure in hypertensive rats. Analysis of their gut microbiota reveals significant improvement in diversity and abundance, which indicates restored metabolism and biosynthesis‐related functions. Pathological analysis of intestine and hypothalamic paraventricular nucleus also shows improvements. In conclusion, VC influences the gut microbiota in achievement of its anti‐hypertensive effects.
To address the significance of enhancing myelination for functional recovery after white matter injury (WMI) in preterm infants, we characterized hypomyelination associated with chronic hypoxia and ...identified structural and functional deficits of excitatory cortical synapses with a prolonged motor deficit. We demonstrate that genetically delaying myelination phenocopies the synaptic and functional deficits observed in mice after hypoxia, suggesting that myelination may possibly facilitate excitatory presynaptic innervation. As a gain-of-function experiment, we specifically ablated the muscarinic receptor 1 (M1R), a negative regulator of oligodendrocyte differentiation in oligodendrocyte precursor cells. Genetically enhancing oligodendrocyte differentiation and myelination rescued the synaptic loss after chronic hypoxia and promoted functional recovery. As a proof of concept, drug-based myelination therapies also resulted in accelerated differentiation and myelination with functional recovery after chronic hypoxia. Together, our data indicate that myelination-enhancing strategies in preterm infants may represent a promising therapeutic approach for structural/functional recovery after hypoxic WMI.
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•Chronic hypoxia causes hypomyelination, synaptic loss, and functional deficits•Hypomyelination results in synaptic and functional deficits•Enhancing myelination rescues hypoxia-induced synaptic and functional deficits•Myelination-enhancing drugs improve functional recovery against hypoxia
Wang et al. demonstrate that hypomyelination specifically contributes to the significant loss of excitatory synapses and prolonged functional deficits after chronic hypoxia and that myelination-enhancing strategies represent a promising approach for functional recovery following hypoxic WMI.
Background and Aim
Previous smaller meta‐analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) ...versus entecavir (ETV) provided controversial results. This updated meta‐analysis aimed to reliably identify any difference in the HCC incidence between TDF‐treated or ETV‐treated CHB patients in general or in specific subgroups.
Methods
PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF‐treated and ETV‐treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random‐effects model.
Results
Twenty‐four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval CI: 0.67–0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72–0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71–0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58–1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66–0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65–0.84; 18 studies).
Conclusion
Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.
Summary Background The mcr-1 gene confers transferable colistin resistance. mcr-1 -positive Enterobacteriaceae (MCRPE) have attracted substantial medical, media, and political attention; however, so ...far studies have not addressed their clinical impact. Herein, we report the prevalence of MCRPE in human infections and carriage, clinical associations of mcr-1 -positive Escherichia coli (MCRPEC) infection, and risk factors for MCRPEC carriage. Methods We undertook this study at two hospitals in Zhejiang and Guangdong, China. We did a retrospective cross-sectional assessment of prevalence of MCRPE infection from isolates of Gram-negative bacteria collected at the hospitals from 2007 to 2015 (prevalence study). We did a retrospective case-control study of risk factors for infection and mortality after infection, using all MCRPEC from infection isolates and a random sample of mcr-1 -negative E coli infections from the retrospective collection between 2012 and 2015 (infection study). We also did a prospective case-control study to assess risk factors for carriage of MCRPEC in rectal swabs from inpatients with MCRPEC and mcr-1 negative at the hospitals and collected between May and December, 2015, compared with mcr-1 -negative isolates from rectal swabs of inpatients (colonisation study). Strains were analysed for antibiotic resistance, plasmid typing, and transfer analysis, and strain relatedness. Findings We identified 21 621 non-duplicate isolates of Enterobacteriaceae, Acinetobacter spp, and Pseudomonas aeruginosa from 18 698 inpatients and 2923 healthy volunteers. Of 17 498 isolates associated with infection, mcr-1 was detected in 76 (1%) of 5332 E coli isolates, 13 (<1%) of 348 Klebsiella pneumoniae , one (<1%) of 890 Enterobacter cloacae , and one (1%) of 162 Enterobacter aerogenes . For the infection study, we included 76 mcr-1 -positive clinical E coli isolates and 508 mcr-1 -negative isolates. Overall, MCRPEC infection was associated with male sex (209 41% vs 47 63%, adjusted p=0·011), immunosuppression (30 6% vs 11 15%, adjusted p=0·011), and antibiotic use, particularly carbapenems (45 9% vs 18 24%, adjusted p=0·002) and fluoroquinolones (95 19% vs 23 30%, adjusted p=0·017), before hospital admission. For the colonisation study, we screened 2923 rectal swabs from healthy volunteers, of which 19 were MCRPEC, and 1200 rectal swabs from patients, of which 35 were MCRPEC. Antibiotic use before hospital admission (p<0·0001) was associated with MCRPEC carriage in 35 patients compared with 378 patients with mcr-1-negative E coli colonisation, whereas living next to a farm was associated with mcr-1-negative E coli colonisation (p=0·03, univariate test). mcr-1 could be transferred between bacteria at high frequencies (10−1 to 10−3 ), and plasmid types and MCRPEC multi-locus sequence types (MLSTs) were more variable in Guangdong than in Zhejiang and included the human pathogen ST131. MCRPEC also included 17 unreported ST clades. Interpretation In 2017, colistin will be formally banned from animal feeds in China and switched to human therapy. Infection with MRCPEC is associated with sex, immunosuppression, and previous antibiotic exposure, while colonisation is also associated with antibiotic exposure. MLST and plasmid analysis shows that MCRPEC are diversely spread throughout China and pervasive in Chinese communities. Funding National Key Basic Research Program of China, National Natural Science Foundation of China/Zhejiang, National Key Research and Development Program, and MRC, UK.
Background
Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non‐Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not ...uniform between countries or regions within Asia and China, and Asian patient‐specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China.
Methods
A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan‐Meier method coupled with the log‐rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0.
Results
The median age of the cohort was 60.0 years with a male‐to‐female ratio of 3.36:1. Five‐year progression‐free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High‐intermediate/high‐risk group according to MIPI‐c, without high‐dose cytarabine, lack of Auto‐SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high‐intermediate/high risk group according to MIPI‐c, without high‐dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA.
Conclusions
First‐line high dose cytarabine exposure, auto‐SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.
Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one ...of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.
A simple and efficient synthesis of NBN‐doped conjugated polycyclic aromatic hydrocarbons (such as diazaborinines) has been accomplished by a catalyst‐free intermolecular dehydration reaction at room ...temperature between boronic acid and diamine moieties with yields up to 99 %. Polycyclic aromatic hydrocarbons with a six‐membered NBN ring are a new class of aggregation‐induced emissive luminogens. Extremely sensitive detection of ppb levels of TNT by phenyl naphthodiazaborinine is straightforward. Visual detection of TNT is illustrated by fabrication of TNT test strips, which can detect as little as 100 ng of TNT powder. This simple and sensitive detection of TNT has potential applications in the area of public safety and security against terrorist activities.
Sensitive to explosives: A simple and efficient room‐temperature, catalyst‐free dehydration method is reported for the synthesis of NBN‐doped polycyclic aromatic hydrocarbons. These contain naphthodiazaborinines, a new class of AIEgen capable of detection of TNT at the ppb level.
•ACE2 are highly expressed in human small intestinal enterocytes.•2019-nCoV may have same tissue tropism such as small intestine with SARS-CoV.•The gastrointestinal tract may be an alternative route ...for 2019-nCoV.•Distribution pattern of ACE2 gene insinuates the possibility of a fecal–oral transmission for COVID-19.
The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients’ stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.
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