Explore the vast range of titles available.

The melting of a solid, like other first-order phase transitions, exhibits an intrinsic time-scale disparity: The time spent by the system in metastable states is orders of magnitude longer than the transition times between the states. Using rare-event sampling techniques, we find that melting of representative solids—here, copper and aluminum—occurs via multiple, competing pathways involving the formation and migration of point defects or dislocations. Each path is characterized by multiple barrier-crossing events arising from multiple metastable states within the solid basin. At temperatures approaching superheating, melting becomes a single barrier-crossing process, and at the limit of superheating, the melting mechanism is driven by a vibrational instability. Our findings reveal the importance of nonlocal behavior, suggesting a revision of the perspective of classical nucleation theory.

AbstractObjectiveTo examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19).DesignCross sectional study.SettingFour hospitals in Wuhan, China.Participants420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing.Main outcome measuresCovid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples.ResultsThe average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%).ConclusionBefore a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.

Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

Obesity is a major public health problem. Regulating food intake and promoting metabolism of fat are two important options for treating obesity. Auricular vagus nerve stimulation (AVNS) is considered as an alternative approach to vagal nerve stimulation. The aim of this study was to investigate the effects of AVNS and its mechanisms on obesity in obese rats. Male Sprague-Dawley rats were fed either a high-fat diet (HFD) or a normal diet for 8 wk. Qualified HFD rats were randomly divided into three groups: the HFD group, the AVNS group, and the sham group for 6 wk treatment. Body weight and daily energy intake were recorded weekly. The rats were sacrificed for measurement of weight of bilateral perirenal, epididymal white adipose tissue (WAT), dorsal brown adipose tissue (BAT), and gastric emptying. Serum cholecystokinin (CCK), peptide YY3 to 36 (PYY3–36) and norepinephrine (NE) were assayed by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction was used to assess the mRNA expressions of CCK subtype receptor a (CCKa) in the antrum, PYY3–36 receptor in the distal ileum, β3-adrenoceptor, and uncoupling protein gene 1 (UCP1) in the BAT. Compared with HFD group, AVNS significantly reduced body weight and epididymal WAT and increased BAT weight, serum NE, mRNA expressions of β3-adrenoceptors, and UCP1 of the BAT, but had no effect on daily energy intake, perirenal WAT weight, gastric emptying, serum levels of CCK and PYY, or mRNA expressions of CCKa receptor and PYY3–36 receptor in the relevant tissues. The sham group, as a comparison group for AVNS, saw less effect in any of the indexes compared with the HFD group. AVNS had more effect on weight loss, reduction of perirenal WAT, and increase of NE, β3-adrenoceptor, and UCP1 than sham. AVNS was more effective in reducing body weight and causing visceral fat loss. Biochemical tests found more NE released in the serum and more β3-adrenoceptor and UCP1 expression in the BAT. All of these features suggested that energy expenditure might play an important role in obesity management by AVNS. •To our knowledge, this is the first study to examine auricular vagal nerve stimulation (AVNS) in obese rats.•We found AVNS affected weight management by energy expenditure but not by food intake.•Relevant indexes of fat metabolism, including norepinephrine, β3-adrenoceptor, and uncoupling protein gene 1 in brown adipose tissue were significantly enhanced by AVNS.

Ten previously undescribed pyrrolidine alkaloids, namely penicipyrrolidines O–X (1–10), were isolated from the mangrove-derived fungus Penicillium sp. DM27, along with five known compounds (11–15). Their structures were determined by comprehensive analysis of HRESIMS and NMR spectroscopic data, and the absolute configurations were established based on biosynthetic considerations and TDDFT-ECD calculations. All isolates were evaluated for their glucose uptake capacity. Notably, penicipyrrolidine P (2) significantly enhanced cellular glucose uptake in L6 myotubes by 3.83-fold, demonstrating activity comparable to that of metformin, whereas penicipyrrolidines Q and R (3 and 4) showed relatively weaker effects.

Human activity intensity is a synthesis index for describing the effects and influences of human activities on land surface. This paper presents the concept of human activity intensity of land surface and construction land equivalent, builds an algorithm model for human activity intensity, and establishes a method for converting different land use/cover types into construction land equivalent as well. An application in China based on the land use data from 1984 to 2008 is also included. The results show that China＇s human activity intensity rose slowly before 2000, while rapidly after 2000. It experienced an increase from 7.63% in 1984 to 8.54% in 2008. It could be generally divided into five levels： Very High, High, Medium, Low, and Very Low, according to the human activity intensity at county level in 2008, which is rated by above 27%, 16%-27%, 10%-16%, 6%-10%, and below 6%. China＇s human activity intensity was spatially split into eastern and western parts by the line of Helan Mountains-Longmen Mountains-Jinghong. The eastern part was characterized by the levels of Very High, High, and Medium, and the levels of Low and Very Low were zonally distributed in the mountainous and hilly areas. In contrast, the western part was featured by the Low and Very Low levels, and the levels of Medium and High were scattered in Gansu Hexi Corridor, the east of Qinghai, and the northern and southern slopes of Tianshan Mountains in Xinjiang.

The theoretically predicted volcano plot for hydrogen production shows the best catalyst as the one that ensures that the hydrogen binding step is thermodynamically neutral. However, the experimental realization of this concept has suffered from the inherent surface heterogeneity of solid catalysts. It is even more challenging for molecular catalysts because of their complex chemical environment. Here, we report that the thermoneutral catalyst can be prepared by simple doping of a platinum atom into a molecule-like gold nanocluster. The catalytic activity of the resulting bimetallic nanocluster, PtAu 24 (SC 6 H 13 ) 18 , for the hydrogen production is found to be significantly higher than reported catalysts. It is even better than the benchmarking platinum catalyst. The molecule-like bimetallic nanocluster represents a class of catalysts that bridge homogeneous and heterogeneous catalysis and may provide a platform for the discovery of finely optimized catalysts. Volcano plots for electrocatalytic hydrogen production show the best catalysts as those ensuring the hydrogen binding step is thermodynamically neutral. Here, the authors report fabrication of a highly active thermoneutral electrocatalyst via doping of a single platinum atom into a gold nanocluster.

Purpose This study aimed to evaluate the role of social participation in the relationship between internet use and depressive symptoms among Chinese older adults and investigate how the internet use interact with social participation to reduce the risk of depressive symptoms. Methods Based on the survey from the China Health and Retirement Longitudinal Study (CHARLS) in 2018, we identified 4645 subjects and used the Ordinary Least Square method (OLS) and Propensity Score Matching method (PSM) to identify the association between Internet use and depression of older people, and further test how social participation played a role in the relationship. Results The level of depression of older people was significantly reduced in those who using internet in China, and the effect was still robust under different identification methods. The mental health was improved when using internet because of the increase of social participation and social capital. Further, The positive effect was stronger especially in those who were female, living in rural areas, has low education attainments and were 70–79 years old. Conclusions The popularity of internet use has a positive effect on the depressive symptoms of Chinese older adults. Effective measures were encouraged to improve the friendliness of internet for older people and promote the popularization of the Internet and older group, achieving the spiritual well-being of them in the Internet society.

Leveraging the conserved cancer genomes across mammals has the potential to transform driver gene discovery in orphan cancers. Here, we combine cross-species genomics with validation across human–dog–mouse systems to uncover a new bone tumor suppressor gene. Comparative genomics of spontaneous human and dog osteosarcomas (OS) expose Disks Large Homolog 2 (DLG2) as a tumor suppressor candidate. DLG2 copy number loss occurs in 42% of human and 56% of canine OS. Functional validation through pertinent human and canine OS DLG2 -deficient cell lines identifies a regulatory role of DLG2 in cell division, migration and tumorigenesis. Moreover, osteoblast-specific deletion of Dlg2 in a clinically relevant genetically engineered mouse model leads to acceleration of OS development, establishing DLG2 as a critical determinant of OS. This widely applicable cross-species approach serves as a platform to expedite the search of cancer drivers in rare human malignancies, offering new targets for cancer therapy.