Search

As one of the first characteristics of cancer cells, chromosomal aberrations during cell division have been well documented. Aneuploidy is a feature of most cancer cells accompanied by an elevated rate of mis-segregation of chromosomes, called chromosome instability (CIN). Aneuploidy causes ongoing karyotypic changes that contribute to tumor heterogeneity, drug resistance, and treatment failure, which are considered predictors of poor prognosis. Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, and its genome map shows extensive aneuploid changes. Elucidating the role of aneuploidy in the pathogenesis of LC will reveal information about the key factors of tumor occurrence and development, help to predict the prognosis of cancer, clarify tumor evolution, metastasis, and drug response, and may promote the development of precision oncology. In this review, we describe many possible causes of aneuploidy and provide evidence of the role of aneuploidy in the evolution of LC, providing a basis for future biological and clinical research.

SEM (A) and TEM (B) images of NTMCu-MOFs.

Yan X, Liu SM, Liu C. Onco Targets Ther. 2022;15:1355–1368 The authors have advised that Xing Yan and Shan Mei Liu should be considered as equally contributed authors for this paper titled “Clinical Applications of Aneuploidies in Evolution of NSCLC Patients: Current Status and Application Prospect” published in OncoTargets and Therapy on November 10, 2022. The updated author list should read as follows: Xing Yan1,* Shan Mei Liu2,*, Changhong Liu1 1The Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, People’s Republic of China; 2Inner Mongolia Medical University, Hohhot, 150110, People’s Republic of China Correspondence: Changhong Liu, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, People’s Republic of China, Tel +86 17709870870, Email 17709870870@163.com *These authors contributed equally to this work The authors apologize for this oversight.

Lentiviral vectors are one of the most commonly used viral delivery systems for gene therapy. Vesicular stomatitis virus-G envelope glycoprotein (VSV G)-pseudotyped lentiviral vectors have been widely used in clinical studies for treatment of virus infections and genetic deficient diseases. However, the efficiency of lentiviral vector transduction has been long recognized as a limiting factor in clinical gene therapy application, especially in transducing hematopoietic stem cells. MARCH8 (membrane-associated RING-CH 8), an E3 ubiquitin ligase, has been reported to target and downregulate VSV G. Results in this study show that MARCH8 induces ubiquitination and lysosome degradation of VSV G, and knockout of MARCH8 in virus-producing cells increases lentiviral vector transduction by elevating the level of VSV G protein. We then engineered VSV G mutant that has the lysine residues in the cytoplasmic domain substituted for arginine, and showed that this G mutant resists degradation by MARCH8, and allows the enhancement of transduction efficiency of lentiviral vector particles than the parental VSV G protein. This engineered VSV G mutant thus further advances the lentiviral vector system as a powerful tool in gene therapy.

Purpose To examine a screen model for detecting undergraduates with higher risk for developing psychosis (HRDP). Design and methods A cross-sectional design with convenience sampling was used. The screen model included exploration stage by self-report scales and confirmation stage by face-to-face interviews. Findings A total of 273 students were detected from 4744 surveys during 4 years. Of them, 120 students with HRDP were identified and 7 had been diagnosed as schizophrenia or bipolar disorders at 12-month follow-up. Practice implications This screen model can be used in early detection for undergraduates with HRDP from large general samples.

Objective Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the l - arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO3−–NO2−–NO) pathway was rarely investigated. Therefore, the aim of this study was to evaluate the effects and mechanisms of action of CR in coronary artery disease (CAD). Methods The NO3−, NO2− and NO levels were examined in the NO3−–NO2−–NO pathway. High-performance ion chromatography was used to quantify NO3− and NO2− levels. Then, NO was quantified using a multifunctional enzyme marker with a fluorescent probe. The tension of aortic rings was measured using a multi myograph system. Results High content of NO3− and low content of NO2− was found in CR, and which could potently convert NO3− to NO2− in the presence of endogenous reductase enzyme. Incubating human coronary artery endothelial cells (HCAECs) with CR-containing serum showed that CR significantly decreased the NO3− content and increased the levels of NO2− and NO in the cells under hypoxic conditions. In addition, CR significantly relaxed isolated aortic rings when the l - arginine –NO pathway was blocked. The optimal concentration of CR for relaxation was 200 mg/mL. Conclusion CR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO3−–NO2−–NO pathway, thereby making up for the deficiency caused by the lack of NO after the l - arginine-NO pathway is suppressed. This study also supports the potential use of a traditional Chinese herb for future drug development.

Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines provide essential tools for the control of the COVID-19 pandemic. A number of technologies have been employed to develop SARS-CoV-2 vaccines, including the inactivated SARS-CoV-2 particles, mRNA to express viral spike protein, recombinant spike proteins, and viral vectors. Here, we report the use of the vaccinia virus Tiantan strain as a vector to express the SARS-CoV-2 spike protein. When it was used to inoculate mice, robust SARS-CoV-2 spike protein-specific antibody response and T-cell response were detected. Sera from the vaccinated mice showed strong neutralizing activity against the ancestral Wuhan SARS-CoV-2, the variants of concern (VOCs) B.1.351, B.1.617.2, and the emerging B.1.1.529 (omicron). This finding supports the possibility of developing a new type of SARS-CoV-2 vaccine using the vaccinia virus vector.

Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages.

Some functional microorganisms in the soil immobilize heavy metals by adsorption and precipitation, prevent the absorption of heavy metals by crops, and play an important role in the passivation and remediation of medium and mild heavy metal-contaminated soil. A pot experiment was conducted to study the effects of the exogenous polyamine-producing bacterium

The high incidence of lymphatic metastasis is closely related to poor prognosis and mortality in cancers. Potent inhibitors to prevent pathological lymphangiogenesis and lymphatic spread are urgently needed. The VEGF-C-VEGFR3 pathway plays a vital role in driving lymphangiogenesis and lymph node metastasis. In addition, COX2 in tumor cells and tumor-associated macrophages (TAMs) facilitates lymphangiogenesis. We recently reported that aiphanol, a natural stilbenolignan, attenuates tumor angiogenesis by repressing VEGFR2 and COX2. In this study, we evaluated the antilymphangiogenic and antimetastatic potency of aiphanol using in vitro, ex vivo and in vivo systems. We first demonstrated that aiphanol directly bound to VEGFR3 and blocked its kinase activity with an half-maximal inhibitory concentration (IC

BackgroundMusculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.ObjectivesTo investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.MethodsWe enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.ResultsTwo hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.ConclusionsThe lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Additional file 3. Figure S2. The expression of 8-FIRLs in normal and OC samples. (a) The expression of AC138904.1; (b)The expression of AP005205.2; (c) The expression of AC007114.1; (d) The expression of LINC00665; (e) The expression of UBXN10-AS1; (f) The expression of AC083880.1; (g) The expression of LINC01558; (h) The expression of AL023583.1; *P < 0.05; **P < 0.01; ***P < 0.001.

Additional file 1. Table S1. A list of FIRGs

Additional file 2. Figure S1. Calibration curve of nomogram. (a-b) Calibration curve of nomogram based on FIRLs signature for OS prediction at 1 year (a), 3 year (b) , and 5 year (c) in the training set; (d-f) Calibration curve of nomogram based on FIRLs signature for OS prediction at 1 year (d), 3 year (e), and 5 year (f) in the testing set.

CRISPR-Cas provides bacteria and archaea with immunity against invading phages and foreign plasmid DNA and has been successfully adapted for gene editing in a variety of species. The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Here we report the repurposing of CRISPR-Cas13a to inhibit human immunodeficiency virus type 1 (HIV-1) infection through targeting HIV-1 RNA and diminishing viral gene expression. We observed strong inhibition of HIV-1 infection by CRISPR-Cas13a in human cells. We showed that CRISPR-Cas13a not only diminishes the level of newly synthesized viral RNA, either from the transfected plasmid DNA or from the viral DNA, which is integrated into cellular DNA, but it also targets and destroys the viral RNA that enters cells within viral capsid, leading to strong inhibition of HIV-1 infection. Together, our results suggest that CRISPR-Cas13a provides a potential novel tool to treat viral diseases in humans., Graphical Abstract, The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Yin et al. demonstrate that CRISPR-Cas13a targets and cleaves the HIV RNA genome and mRNA, leading to strong inhibition of HIV-1 infection.

Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505-527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515-519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.

2D transition metal carbides or nitrides, known as MXenes, are a new family of 2D materials with close to 30 members experimentally synthesized and dozens more theoretically investigated. Because o...

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-β-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.通过尿生物标志物进行早期诊断和无创性预测对于预防糖尿病肾病(DKD)的进展是重要的，但是，也是有争议的。既往的研究显示，尿肾小管生物标志物(UTBs)与DKD患者中医证候之间有潜在的联系。因此，我们进一步评价尿生物标志物的联合检测在无创性预测早期DKD肾气虚证患者肾损伤程度中的临床意义，并初步揭示UTBs与DKD中医证候之间的潜在生物学联系。将92例2型糖尿病患者分为以下3组，正常白蛋白尿组20例患者，微量白蛋白尿组50例患者，大量白蛋白尿组22例患者。我们发现，在各组患者中，24hUAlb和UACR呈现出逐步而明显的升高。尿胱抑素C(UCysC)、尿N-乙酰1-β-D-氨基葡萄糖苷酶(UNAG)和尿视黄醇结合蛋白(URBP)均显示出逐渐的升高，这与各组患者白蛋白尿的程度相一致。而且，24hUAlb、UACR 与 UCysC、UNAG 和 URBP 分别呈正相关。在72例伴有白蛋白尿的2型DKD患者中，UNAG与URBP呈正相关，UCysC也与UNAG、URBP分别呈正相关。此外，所有患者的中医证候分布特征均与肾气虚证的临床表现相一致。因此，UCysC、UNAG、URBP和UAlb的联合检测可作为一项无创性预测早期2型DKD肾气虚证患者肾损伤程度的实用临床技术。UTBs可能是DKD患者特定中医证候的生物学基础之一。.

SARS-CoV-2 has become a global threat to public health. Infected individuals can be asymptomatic or develop mild to severe symptoms, including pneumonia, respiratory distress, and death. This wide spectrum of clinical presentations of SARS-CoV-2 infection is believed in part due to the polymorphisms of key genetic factors in the population. In this study, we report that the interferon-induced antiviral factor IFITM3 inhibits SARS-CoV-2 infection by preventing SARS-CoV-2 spike-protein-mediated virus entry and cell-to-cell fusion. Analysis of a Chinese COVID-19 patient cohort demonstrates that the rs12252 CC genotype of IFITM3 is associated with SARS-CoV-2 infection risk in the studied cohort. These data suggest that individuals carrying the rs12252 C allele in the IFITM3 gene may be vulnerable to SARS-CoV-2 infection and thus may benefit from early medical intervention.

SERINC5 is a multi-span transmembrane protein that is incorporated into HIV-1 particles in producing cells and inhibits HIV-1 entry. Multiple retroviruses like HIV-1, equine infectious anemia virus and murine leukemia virus are subject to SERINC5 inhibition, while HIV-1 pseudotyped with envelope glycoproteins of vesicular stomatitis virus and Ebola virus are resistant to SERINC5. The antiviral spectrum and the underlying mechanisms of SERINC5 restriction are not completely understood. Here we show that SERINC5 inhibits influenza A virus infection by targeting virus-cell membrane fusion at an early step of infection. Further results show that different influenza hemagglutinin (HA) subtypes exhibit diverse sensitivities to SERINC5 restriction. Analysis of the amino acid sequences of influenza HA1 strains indicates that HA glycosylation sites correlate with the sensitivity of influenza HA to SERINC5, and the inhibitory effect of SERINC5 was lost when certain HA glycosylation sites were mutated. Our study not only expands the antiviral spectrum of SERINC5, but also reveals the role of viral envelope glycosylation in resisting SERINC5 restriction.

Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements. Author summary Retrotransposons occupy more than 40% of human genome, and have co-evolved with humans for millions of years. Long interspersed element type 1 (LINE-1, or L1) is the only retrotransposon that is able to jump to a new locus. LINE-1 retrotransposition causes genome instability, and is associated with genetic diseases including autoimmune diseases and cancer. To suppress this genome toxicity caused by LINE-1, humans have developed multi-layered mechanisms to control LINE-1 activity. MxB has been previously shown to inhibit LINE-1 mobility, thus contributing to host restriction of LINE-1. Here, we further demonstrate that MxB effectively restricts LINE-1 retrotransposition by sequestering LINE-1 ribonucleoprotein (RNP) within the cytoplasmic stress granules, thus guards genome stability. Hence our data attribute the restriction function of MxB to sequestering LINE-1 RNP to stress granules.

BackgroundThere have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study.MethodsFrom August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods.ResultsOverall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole.ConclusionThe continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

Developing high-performance and reusable adhesives from renewable feedstocks is of significance to sustainable development, yet it still remains a formidable task. Herein, castor oil, melevodopa, and iron ions are used as building blocks to construct a novel bio-based supramolecular adhesive (BSA) with outstanding adhesion performances. It is prepared through partial coordination between melevodopa functionalized castor oil and Fesup3+/supions. Noncovalent interactions between adherends and the catechol unit from melevodopa contribute to reinforcing adhesion, and the metal-ligand coordination between catechol and Fesup3+/supions is utilized to strengthen cohesion. By combining strong adhesion and tough cohesion, the prepared BSA achieves an adhesion strength of 14.6 MPa at ambient temperature, a record-high value among reported bio-based adhesives as well as supramolecular adhesives to the best of knowledge. It also outperforms those adhesives at cryogenic temperature, realizing another record-high adhesion strength of 9.5 MPa at -196 °C. In addition, the BSA displays excellent multi-reusability with more than 87% of the original adhesion strength remaining even after reuse for ten times. It is highly anticipated that this line of research will provide a new insight into designing bio-based adhesives with outstanding adhesion performances and excellent multi-reusability.

Flipped learning is an instructional model with core features of pre-class learning followed by in- class practice of knowledge through active and collaborative learning. However, non-compliance with pre-class activities is a commonly cited challenge in flipped learning, where a lack of student engagement leads to insufficient pre-class preparation, diminishing flipped learning’s intended benefits significantly as the students will then not participate well in the in-class activities. It lends consideration to the potential obstacles and solutions in increasing students’ engagement in pre-class learning, paving the way to pre-class learning compliance to achieve the full potential of flipped learning in improving students’ learning outcomes. This study uses systematic literature review with qualitative content analysis to identify three main areas, namely technological, pedagogical, and student perceptions, to instil optimal conditions to promote pre-class engagement and preparation.

Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries. Hypothesis/Gap Statement. To better understand the epidemiological trends and characteristics of CRE in the Henan province. Aim. We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China. Methodology. A total of 305 CRE isolates were subjected to multiple tests, including in vitro antimicrobial susceptibility testing, PCR for carbapenemase genes bla KPC, bla NDM, bla IMP, bla VIM, bla OXA-48-like. Tigecycline-resistant genes ramR, oqxR, acrR, tetA, rpsJ, tetX, tetM, tetL were analysed in five tigecycline non-susceptible carbapenem-resistant Klebsiella pneumoniae isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant K. pneumoniae (CRKP). Results. The most common CRE species were K. pneumoniae (234, 77 %), Escherichia coli (36, 12 %) and Enterobacter cloacae (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % bla KPC, 13 % bla NDM, 6 % bla IMP, and 1 % combined bla KPC/bla NDM genes. K. pneumoniae carbapenemase (KPC) was the predominant carbapenemase in K. pneumoniae (87 %), whereas NDM and IMP were frequent in E. coli (53 %) and E. cloacae (69 %), respectively. Mutations in the ramR, tetA, and rpsJ genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among K. pneumoniae strains. Conclusion. A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant K. pneumonia isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.

Introduction Carbapenem-resistant Enterobacteriaceae (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries. Hypothesis/Gap Statement To better understand the epidemiological trends and characteristics of CRE in the Henan province. Aim We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China. Methodology A total of 305 CRE isolates were subjected to multiple tests, including in vitro antimicrobial susceptibility testing, PCR for carbapenemase genes bla KPC, bla NDM, bla IMP, bla VIM, bla OXA-48-like. Tigecycline-resistant genes ramR, oqxR, acrR, tetA, rpsJ, tetX, tetM, tetL were analysed in five tigecycline non-susceptible carbapenem-resistant Klebsiella pneumoniae isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant K. pneumoniae (CRKP). Results The most common CRE species were K. pneumoniae (234, 77 %), Escherichia coli (36, 12 %) and Enterobacter cloacae (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % bla KPC, 13 % bla NDM, 6 % bla IMP, and 1 % combined bla KPC/bla NDM genes. K. pneumoniae carbapenemase (KPC) was the predominant carbapenemase in K. pneumoniae (87 %), whereas NDM and IMP were frequent in E. coli (53 %) and E. cloacae (69 %), respectively. Mutations in the ramR, tetA, and rpsJ genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among K. pneumoniae strains. Conclusion A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant K. pneumonia isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.

Additional file 3: Table S3. Logistic regression analysis of clinical characteristics associated with clinical remission at 1-year for the total population.

Additional file 2: Table S2. Absolute and percent changes in β cell function at 1-year for subgroups based on DK/DKA history. Data are shown as means ± S.D. DK, diabetic ketosis; DKA, diabetic ketoacidosis.

Additional file 1: Table S1. Absolute and percent changes in β cell function at 1-year for the total population and age-based subgroups. Data are shown as means ± S.D. FCP, fasting C-peptide; PCP, 2-h postprandial C-peptide. ΔFCP ratio was defined as the calibration of changed FCP at 1-year follow-up by its baseline level; ΔPCP ratio was defined as the calibration of changed PCP at 1-year follow-up by its baseline level.

Background: Recently, diabetic nephropathy (DN) becomes a common health problem in China as one of the major microvascular complications of diabetes mellitus. Therefore, the incipient diagnosis and noninvasive detections in clinic by the association of urinary biomarkers are important for preventing the progress of DN. However, the clinical significance of urinary biomarkers is controversial nowadays. This study thereby aimed to further evaluate the clinical significance of the association of urinary biomarkers in noninvasively predicting the renal damaged extent of the early type 2 DN patients with kidney qi deficiency syndrome in an integrated traditional and western medical center, and preliminarily confirm the correlation between urinary tubular biomarkers and the biological bases of DN patients.Methods: Ninety-two patients in an integrated traditional and western medical center of China were categorized into 3 groups, 20 patients with normo-albuminuria, 50 patients with micro-albuminuria, and 22 patients with macro-albuminuria. In addition to urinary albumin (UAlb) and urinary albumin-to-creatinine ratio (UACR), serum creatinine, estimated glomerular filtration rate and various urinary tubular biomarkers were tested respectively. Besides, clinical characteristics and kidney asthenia syndrome distribution in all patients were observed. Results: In these 3 groups, 24-h UAlb and UACR showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acety1-β-D-glucosaminidase (UNAG) and urinary retinal binding protein (URBP) synchronously showed gradual increases consistent with albuminuria degree in 3 groups. Moreover, 24-h UAlb and UACR were positively correlated with UCysC, UNAG and URBP. In the 72 DN patients with albuminuria, there was a positive correlation between UNAG and URBP, and UCysC was also positively correlated with UNAG and URBP. Additionally, TCM syndrome distributional characteristics in all patients were consistent with the clinical manifestations of kidney qi deficiency syndrome. Conclusion: In this investigation, we ulteriorly demonstrated that the association within UCysC, UNAG, URBP and UAlb may be used as practical targets in noninvasively forecasting the extent of renal injury in the early type 2 DN patients with kidney qi deficiency syndrome. More importantly, we found that urinary tubular biomarkers may be one of the biological bases of DN patients with the specific traditional Chinese medicine syndrome.

2D PbS nanoplatelets (NPLs) form an emerging class of photoactive materials and have been proposed as robust materials for high-performance optoelectronic devices. However, the main drawback of PbS NPLs is the large lateral size, which inhibits their further investigations and practical applications. In this work, ultra-small 2D PbS NPLs with uniform lateral size (11.2 ± 1.7 nm) and thickness (3.7 ± 0.9 nm, ≈6 layers) have been successfully fabricated by a facile liquid-phase exfoliation approach. Their transient optical response and photo-response behavior are evaluated by femtosecond-resolved transient absorption and photo-electrochemical (PEC) measurements. It is shown that the NPLs-based photodetectors (PDs) exhibit excellent photo-response performance from UV to the visible range, showing extremely high photo-responsivity (27.81 mA W-1 ) and remarkable detectivity (3.96 × 1010 Jones), which are figures of merit outperforming currently reported PEC-type PDs. The outstanding properties are further analyzed based on the results of first-principle calculations, including electronic band structure and free energies for the oxygen evolution reaction process. This work highlights promising applications of ultra-small 2D PbS NPLs with the potential for breakthrough developments also in other fields of optoelectronic devices.

Most of the studies on the herbThe NOHigh content of NOCR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO

Since their discovery in 2011, MXenes (abbreviation for transition metal carbides, nitrides, and carbonitrides) have emerged as a rising star in the family of 2D materials owing to their unique properties. Although the primary research interest is still focused on pristine MXenes and their composites, much attention has in recent years been paid also to MXenes with diverse compositions. To this end, this work offers a comprehensive overview of the progress on compositional engineering of MXenes in terms of doping and substituting from theoretical predictions to experimental investigations. Synthesis and properties are briefly introduced for pristine MXenes and then reviewed for hetero-MXenes. Theoretical calculations regarding the doping/substituting at M, X, and T sites in MXenes and the role of vacancies are summarized. After discussing the synthesis of hetero-MXenes with metal/nonmetal (N, S, P) elements by in situ and ex situ strategies, the focus turns to their emerging applications in various fields such as energy storage, electrocatalysts, and sensors. Finally, challenges and prospects of hetero-MXenes are addressed. It is anticipated that this review will be beneficial to bridge the gap between predictions and experiments as well as to guide the future design of hetero-MXenes with high performance.

Block copolymer brushes are of great interest due to their rich phase behavior and value-added properties compared to homopolymer brushes. Traditional synthesis involves grafting-to and grafting-from methods. In this work, a recently developed "polymer-single-crystal-assisted-grafting-to" method is applied for the preparation of block copolymer brushes on flat glass surfaces. Triblock copolymer poly(ethylene oxide)-b-poly(l-lactide)-b-poly(3-(triethoxysilyl)propyl methacrylate) (PEO-b-PLLA-b-PTESPMA) is synthesized with PLLA as the brush morphology-directing component and PTESPMA as the anchoring block. PEO-b-PLLA block copolymer brushes are obtained by chemical grafting of the triblock copolymer single crystals onto a glass surface. The tethering point and overall brush pattern are determined by the single crystal morphology. The grafting density is calculated to be ≈0.36 nm-2 from the atomic force microscopy results and is consistent with the theoretic calculation based on the PLLA crystalline lattice. This work provides a new strategy to synthesize well-defined block copolymer brushes.

Abnormal expression of ADAM29 has been frequently reported in several cancers, however, its role in clear cell renal cell carcinoma (ccRCC) has not evaluated in detail. Herein, we attempt to determine the biological role and the action mechanism of ADAM29 in ccRCC. Bioinformatics analysis based on the ccRCC RNA-Seq dataset from TCGA database revealed that ADAM29 was up-expressed in ccRCC tissues by comparison with normal tissues. And a significant increase of ADAM29 expression was also observed in 3 ccRCC cell lines (UT33A, Caki-1, and786-O) in comparison with normal cell line. Besides, high level of ADAM29 was found to be connected with the poor prognosis and could be considered as an independent prognosticator for patients with ccRCC. Furthermore, functional experiments in vitro demonstrated that ADAM29 promoted the growth, invasion and migration of ccRCC cells. Moreover, Western blot assays indicated that ADAM29 was positively correlated with the level of proliferation-related proteins Cyclin D1 and PCNA and motion-related proteins MMP9 and Snail. Our data indicate that ADAM29 acts as an oncogene that increases tumour cells proliferation, invasion and migration partly by regulating the expression of Cyclin D1/PCNA/MMP9/Snail, suggesting that ADAM29 may become a prognosticator and therapeutic candidate for ccRCC.

Cyclic GMP-AMP synthase (cGAS) is a major sensor of cytosolic DNA from invading pathogens and damaged cellular organelles. Activation of cGAS promotes liquid-like phase separation and formation of membraneless cytoplasmic structures. Here, we found that cGAS bound G3BP1, a double-stranded nucleic acid helicase involved in the formation of stress granules. Loss of G3BP1 blocked subcellular cGAS condensation and suppressed the interferon response to intracellular DNA and DNA virus particles in cells. Furthermore, an RNA-dependent association with PKR promoted G3BP1 foci formation and cGAS-dependent interferon responses. Together, these results indicate that PKR promotes the formation of G3BP1-dependent, membraneless cytoplasmic structures necessary for the DNA-sensing function of cGAS in human cells. These data suggest that there is a previously unappreciated link between nucleic acid sensing pathways, which requires the formation of specialized subcellular structures.

The main purpose of this study was to examine the longitudinal mediation effects of multiple gaming motives from online game involvement to problematic Internet use (PIU). In terms of mediators, the present study included three specific gaming motivations - escapism, advancement, and socializing. A sample of 389 gamers participated in the study from freshman to junior college years. Gaming involvement was collected at the freshman year, motives at sophomore, and PIU at junior. Initially, the three gaming motives were examined separately for their longitudinal mediation effects in a series of single-mediator models. Next, the three motives were simultaneously included in a multiple-mediator model to compare the relative levels of their mediation effects from gaming involvement to PIU across a period of two years. In the multiple-mediator model, the most compelling results showed that escapism and advancement were positively associated with PIU, yet socializing was not; socializing failed to significantly predict later PIU. Also, the direct effect of gaming involvement on PIU was weak and failed to reach significant level, contradicting to the findings of previous cross-sectional studies. Many game players experience great pleasure from immersing themselves in a virtual world, and often to the extent of developing addictive symptoms. This phenomenon is referred to as “pull” effect which is considered comparable to the motive of “pursuing in-game advancement” in the present study. Conversely, frustrations or other negative experiences in real life might also bring about a “push” effect that tugs players into gaming. The motive of escapism from the real-life in this study resembles the so-called “push” effect. The authors suggest when gamers demonstrated social motive during game time, such as participating in a gamer community and collaborating with the others despite being socially withdrawn in real life, it would be less reasonably to be regarded as PIU. During game time, if gamers experience a temporary sense of well-being, it might help to vent their real-life frustration. However, an excessive use of this emotion-focused coping strategy might still increase the risk of PIU.

To date the scrolled morphology of γ-phase poly(vinylidene fluoride) (PVDF) has been witnessed via high temperature melt crystallization of crystalline thin films and through imaging of chemical etched PVDF bulk films. Here we show the first growth and characterization of free-standing γ-phase PVDF scrolls via solution crystallization. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy have been used to characterize and to further understand the fundamental preferred crystalline habit of the γ-phase of PVDF.

In recent decades, extensive studies have been devoted to assembling nanoparticles (NPs) into various ordered structures to achieve novel optical properties. However, it still remains a challenging task to assemble NPs into cyclic one-dimensional (1D) shapes, such as rings and frames. Herein, we report a directed assembly method to precisely assemble NPs into well-defined, free-standing frames using polymer single crystals (PSCs) as the template. Preformed poly(ethylene oxide) (PEO) single crystals were used as the template to direct the crystallization of block copolymer (BCP) poly(ethylene oxide)-b-poly(4-vinylpyridine) (PEO-b-P4VP), which directs the gold NPs (AuNPs) to form AuNP frames. By controlling the PSC growth, we were able to, for the first time, precisely tune both the size and width of the AuNP frame. These novel AuNP frames topologically resemble NP nanorings and cyclic polymer chains, and show unique surface plasmon resonance (SPR) behaviors.

Inspired by stimuli-triggered unraveling of the von Willebrand factor from a nonsticky globular to a stretched linear shape with exposure of functional groups in blood clotting, this article reports on the synthesis of thermosensitive binary heterografted linear molecular brushes that exhibit temperature-induced shape changing between extended wormlike and collapsed yet stable globular conformations in water. The molecular brushes are composed of two distinct side chain polymers: thermosensitive poly(ethoxydi(ethylene glycol) acrylate) (PDEGEA), which undergoes a lower critical solution temperature (LCST) transition at 9 °C in water, and poly(ethylene oxide) (PEO), which serves as a stabilizer for the collapsed state. A “grafting to” method was developed to construct molecular brushes by clicking alkyne end-functionalized side chain polymers onto an azide-bearing backbone polymer. While a 1.0 mg/g aqueous solution of PDEGEA homografted molecular brushes turned cloudy upon heating from 0 to 22 °C, at the s...

One of the fundamental laws in crystallization is translational symmetry, which accounts for the profound shapes observed in natural mineral crystals and snowflakes. Herein, we report on the spontaneous formation of spherical hollow crystals with broken translational symmetry in crystalline molecular bottlebrush (mBB) polymers. The unique structure is named as mBB crystalsome (mBBC), highlighting its similarity to the classical molecular vesicles. Fluorescence resonance energy transfer (FRET) experiments show that the mBBC formation is driven by local chain overcrowding-induced asymmetric lamella bending, which is further confirmed by correlating crystalsome size with crystallization temperature and mBBʼs side chain grafting density. Our study unravels a new principle of spontaneous translational symmetry breaking, providing a general route towards designing versatile nanostructures., One of the fundamental laws in crystallization is translational symmetry but breaking translational symmetry can be used as a general route towards the design of nanostructures. Here the authors show that overcrowding in molecular bottlebrush polymers allows for spontaneous formation of spherical hollow crystals with broken translational symmetry.

Nanoparticles can be assembled into complex structures and architectures by using a variety of methods. In this review, we discuss recent progress of using polymer crystallization (particularly polymer single crystals, PSCs) to direct nanoparticle assembly. PSCs have been extensively studied since 1957. Mainly appearing as quasi-two-dimensional (2D) lamellae, PSCs are typically used as model systems to determine polymer crystalline structures, or as markers to investigate the crystallization process. Recent research has demonstrated that they can also be used as nanoscale functional materials. Herein, we show that nanoparticles can be directed to assemble into complex shapes by using in situ or ex situ polymer crystal growth. End-functionalized polymers can crystallize into 2D nanosheet PSCs, which are used to conjugate with complementary nanoparticles, leading to a nanosandwich structure. These nanosandwiches can find interesting applications for catalysis, surface-enhanced Raman spectroscopy, and nanomotors. Dissolution of the nanosandwich leads to the formation of Janus nanoparticles, providing a unique method for asymmetric nanoparticle synthesis.