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Abstract Background Epidemiological studies have confirmed the relationship between personality trait neuroticism and physical health. However, the relationship between neuroticism and frailty remains unconfirmed. This study employed a bi-directional two-sample Mendelian randomization (MR) approach to investigate the causal relationship between neuroticism and frailty. Methods The neuroticism genome-wide association study (GWAS) data from the UK Biobank contained twelve neuroticism-related traits with 489,212 participants. The genetic frailty index data were extracted from the UK Biobank and Swedish TwinGene, involving 175,226 individuals. Independent genetic variants associated with neuroticism and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and MR-PRESSO were mainly used for MR analysis. Results The MR analysis showed a positive causal relationship between neuroticism and the risk of frailty (odds ratio (OR) = 1.627, 95% confidence interval (CI) = 1.538–1.722, P

Two new species, Beaufortia granulopinna and Beaufortia viridis, are described from the upper Pearl River system in southwest China. Both species share the characteristics of the Beaufortia pingi species group, including prominent vertical stripes on the lateral body and pinnate-type lower lips, distinguishing them from other Beaufortia species. Beaufortia granulopinna is differentiated from other species in the group by possessing a unique set of characteristics: the presence of well-developed prominent tubercles on the first 6–9 pectoral fin rays in adults; and a significant proportion (54.76%) of individuals experiencing blurriness or absence of vertical stripes in the mid-section of the lateral body upon reaching adulthood. The minimum interspecific genetic distance within the genus based on mitochondrial cytb gene sequences is 10.80%. Beaufortia viridis is distinguished from other species in the group by consistently exhibiting vertical stripes of uniform length, width, and spacing across all stages of growth; the absence of tubercles on the branched rays of pectoral fins; and a body coloration of dark cyan to green. The minimum interspecific genetic distance within the genus based on mitochondrial cytb gene sequences is 4.60%. Molecular phylogenetic results confirm that the Beaufortia pingi species group forms a monophyletic clade, which is congruent with morphological classification findings. This study also addresses and resolves the taxonomic ambiguity surrounding Beaufortia pingi and Beaufortia zebroida, providing a redescription of these taxa.

Due to the excellent quantum conversion and spectral response characteristics of the AlGaN photocathode, it has become the most promising III-V group semiconductor photocathode in solar-blind signal photoconversion devices in the ultraviolet band. Herein, the influence factors of the time-resolved characteristics of the AlGaN photocathode are researched by solving the photoelectron continuity equation and photoelectron flow density equation, such as the AlN/AlGaN interface recombination rate, AlGaN electron diffusion coefficient, and AlGaN activation layer thickness. The results show that the response time of the AlGaN photocathode decreases gradually with the increase in AlGaN photoelectron diffusion coefficient and AlN/AlGaN interface recombination rate, but the response time of the AlGaN photocathode gradually becomes saturated with the further increase in AlN/AlGaN interface recombination rate. When the thickness of the AlGaN photocathode is reduced from 250 nm to 50 nm, the response time of the AlGaN photocathode decreases from 63.28 ps to 9.91 ps, and the response time of AlGaN photocathode greatly improves. This study provides theoretical guidance for the development of a fast response UV detector.

Abstract Hepatoblastoma, a common extracranial malignant solid tumor in childhood, is often detected at an advanced stage and is difficult to treat surgically. Despite the availability of multiple comprehensive treatments that can be combined with surgery, hepatoblastoma treatment outcomes remain poor. Surgery is the main treatment strategy for hepatoblastoma, but it faces many challenges, including tumor attachment to surrounding tissues, tumor wrapping or invading of vital organs and tissues, the presence of giant or multiple tumors, distant metastasis, the formation of a tumor thrombus, and significant surgical trauma. In this review, we discuss recent research advances and propose potential strategies for overcoming these challenges. Such strategies may improve the rate of hepatoblastoma resection and local control in children, as well as reduce complications and trauma.

ABSTRACTObjective The aim of this study was to investigate the possible causal relationship between COVID-19 and the risk of pre-eclampsia/eclampsia using a Mendelian randomized (MR) design.Methods We estimated their genetic correlations and then performed two-sample Mendelian randomization analyses using pooled statistics from the COVID-19 susceptibility/hospitalization genome-wide association study and the pre-eclampsia/eclampsia datasets. The main analyses were performed using the inverse variance weighting method, supplemented by the weighted median method and the MR-Egger method.Results We identified a significant and positive genetic correlation between COVID-19 susceptibility and pre-eclampsia/eclampsia [OR = 1.23 (1.01–1.51), p = 0.043]. Meanwhile, hospitalization of COVID-19 was significantly associated with a higher risk of pre-eclampsia/eclampsia [OR = 1.15 (1.02–1.30), p = 0.024]. Consistently, hospitalization of COVID-19 were nominally associated with higher risk of pre-eclampsia [OR = 1.14, (1.01–1.30), p = 0.040]. The results were robust under all sensitivity analyses.Conclusion These results suggest that COVID-19 may increase the risk of pre-eclampsia/eclampsia. Future development of preventive or therapeutic interventions should emphasize this to mitigate the complications of COVID-19. [Figure: see text]

Abstract Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS‐CoV‐2 infection via upregulating angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans‐activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS‐CoV‐2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon‐λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS‐CoV‐2 infection by boosting NR4A2‐induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS‐CoV‐2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.

Abstract Super-resolution microscopic imaging employing upconversion nanoparticles is applied to reveal the surface heterogeneity of tumor cell-derived small extracellular vesicles, i.e., exosome. The number of surface antigens of every extracellular vesicles can be quantified by both the high imaging resolution and stable brightness of upconversion nanoparticles. This method proves its great potential in nanoscale biological studies.

The authors report high-efficiency emission depletion through a surface migration emission depletion mechanism, which takes advantage of the effects of surface quenching and energy migration in nanocrystals. They demonstrate super-resolution microscopy with very low depletion saturation intensities.

The authors introduce stimulated-emission induced excitation depletion (STExD) nanoscopy using a single pair of low-power, near-infrared, continue-wave lasers. Emission of multichromatic probes is inhibited by cascade amplified depletion in lanthanide upconversion systems induced by manipulating their common sensitizer.

Abstract Men who have sex with men (MSM) are potentially at high risk for HIV infection, their HIV prevalence far exceeds the national prevalence rate. There are also a number of MSM who have sex with women, mostly unprotected, which can transmit HIV to their female sexual partners and even to the next generation. The purpose of this article is to evaluate the prevalence of heterosexual behaviors in Chinese men who have sex with men and the status of condom utilization as well as HIV infection among MSM with heterosexual behaviors, so as to further improve the investigation and prevention and control of AIDS in MSM population. We systematically searched China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Calligraphy (VIP), Pubmed, and Embase following certain retrieval strategies to find relevant articles published from January 1, 2015 to November 18, 2019, The useful information extracted from qualified articles, Stata 15.1 and Review Manager 5.3 were employed for further meta analysis. The estimated prevalence of heterosexual behaviors among MSM in the past year was 19.0% (95% CI 17.0%, 22.0%). The estimated condom utilization rate of the last heterosexual behavior among MSM and condom adherence rate of heterosexual behaviors among MSM were 51.0% (95% CI 44.0%, 58.0%) and 31.0% (95% CI 25.0%, 38.0%), respectively. And the pooled HIV prevalence in MSM with heterosexual behaviors was 9% (95% CI 6%, 13%). The sensitivity analysis showed that the results were stable. No publication bias was found by Egger’s test. There is a high proportion of MSM with heterosexual behaviors and low condom utilization in China. HIV prevalence in MSM with heterosexual behaviors is also high. Therefore, adequate attention should be given to this particular group and measures should be taken in order to reduce the risk of transmission of HIV from subpopulations to the general population.

Abstract Background The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics. Methods Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package “outbreaker”. The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test. Results From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based sub-clusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became “pure” in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P

Abstract Background Coronavirus disease 2019 (COVID-19) emerged in China in December 2019. The COVID-19 pandemic hindered dental education, as school buildings were closed. Online dental teaching provided an alternative teaching tool for dental education. However, the efficiency of online dental teaching and student preferences for online dental teaching are unclear. Aim To investigate the satisfaction with online dental teaching practices among undergraduate dental students and standardized resident physician training students during the COVID-19 pandemic in China. Methods A total of 104 undergraduate dental students and 57 standardized resident physician training students from Zhejiang University participated in the study. A 12-item survey was conducted. This investigation included the teaching methods received, frequency of classes, degree of satisfaction, preferred teaching method, whether to participate in a course regarding COVID-19 prevention, and the effects of teaching. The percentages were then calculated and evaluated for each item. Results A total of 161 students (104 undergraduate dental students and 57 standardized resident physician training students) participated in this survey. All students had online dental classes during the COVID-19 pandemic. Lecture-based learning (LBL), case-based learning (CBL), problem-based learning (PBL), team-based learning (TBL), and research-based learning (RBL) were selected as teaching methods. Students were more satisfied with LBL and CBL than PBL, RBL, and TBL. The majority of students had more than four classes per week. The most selected protective measures were hand washing, wearing masks, and wearing gloves. A total of 46.6% of students participated in courses on COVID-19. After training, the students consciously chose to wear face shields and protective clothing. Conclusions Dental students accepted online dental learning during the COVID-19 pandemic. Students preferred LBL and CBL and were satisfied with the classes. Courses on COVID-19 helped students understand how to prevent COVID-19 transmission in the dental clinic.

Early diagnosis of acute ST-segment elevation myocardial infarction (STEMI) and early determination of the culprit vessel are associated with a better clinical outcome. We developed three deep learning (DL) models for detecting STEMIs and culprit vessels based on 12-lead electrocardiography (ECG) and compared them with conclusions of experienced doctors, including cardiologists, emergency physicians, and internists. After screening the coronary angiography (CAG) results, 883 cases (506 control and 377 STEMI) from internal and external datasets were enrolled for testing DL models. Convolutional neural network-long short-term memory (CNN-LSTM) (AUC: 0.99) performed better than CNN, LSTM, and doctors in detecting STEMI. Deep learning models (AUC: 0.96) performed similarly to experienced cardiologists and emergency physicians in discriminating the left anterior descending (LAD) artery. Regarding distinguishing RCA from LCX, DL models were comparable to doctors (AUC: 0.81). In summary, we developed ECG-based DL diagnosis systems to detect STEMI and predict culprit vessel occlusion, thus enhancing the accuracy and effectiveness of STEMI diagnosis.

We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) mutations increase the occurrence of hepatocellular carcinoma (HCC) and identify novel putative therapeutic targets. Wild-type HBx (WT-HBx) and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; and Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into Sleeping Beauty (SB) mouse models. The HCC incidence was higher in the M3-HBx- and Ct-HBx-injected SB mice. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. Ectopic expression of M3-HBx and Ct-HBx significantly increased proliferation and S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors by cDNA microarray analysis. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of SB mice. Silencing PAI1 attenuated the effects of M3-HBx and Ct-HBx on the growth of HepG2 and HeLa cells. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a prognostic biomarker and therapeutic target in HBV-related HCC.

According to its incidence patterns, colorectal cancer (CRC) tends to occur more frequently in males than in females, and the evidence shows that CRC is a hormone-related tumor. These findings indicate that androgen receptor (AR) gene methylation might be important for the regulation of the CRC risk in the different sexes. We used a case–control study to investigate the association between AR methylation in peripheral blood (PBL) and CRC risk. A cohort study was conducted to analyze the effect of AR methylation levels in both PBL and tissue on the prognosis of CRC. AR methylation levels were detected using methylation-sensitive high-resolution melting (MS-HRM). The results indicate that the hypomethylation of AR was significantly associated with the risk of CRC (OR = 1.869, 95% CI: 1.629–2.141, P < 0.001), and the results remained similar after adjusting for the propensity score (PS) (OR = 1.344, 95% CI: 1.147–1.575, P < 0.001) and PS matching (OR = 1.138, 95% CI: 1.000–1.292 P = 0.049). The hypomethylation of AR was significantly associated with CRC in males (OR = 2.309, 95% CI: 1.200–4.245; P = 0.012) but not females (OR = 1.000, 95% CI: 0.567–1.765; P = 0.999). The methylation status of AR in PBL and tissue does not seem to be associated with prognosis in colorectal cancer (OR = 1.425, 95% CI: 0.895–2.269, P = 0.135; OR = 0.930, 95% CI: 0.674–1.285, P = 0.661). We conclude that AR hypomethylation in PBL is associated with a high risk of CRC and may serve as a biomarker. Further studies involving large sample sizes are needed to validate the results of this study.

Upconversion nanoparticles, which do not suffer from the photophysical artifacts that limit fluorescent molecules, offer an exciting opportunity for biological super-resolution imaging. Here, Zhan et al. develop an efficient STED mechanism using optimized lanthanide upconversion nanoparticles, enabling cytoskeleton nanoscopic imaging.

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging nanoprobes due to their excellent photostability. As one of the most commonly used lanthanide activators, Tm3+ ions have perfect ladder-type electron configuration and can be directly excited by bio-friendly near-infrared-II (NIR-II) wavelengths. Here, the emission characteristics of Tm3+-doped nanoparticles under laser excitations of different near-infrared-II wavelengths were systematically investigated. The 1064 nm, 1150 nm, and 1208 nm lasers are proposed to be three excitation strategies with different response spectra of Tm3+ ions. In particular, we found that 1150 nm laser excitation enables intense three-photon 475 nm emission, which is nearly 100 times stronger than that excited by 1064 nm excitation. We further optimized the luminescence brightness after investigating the luminescence quenching mechanism of bare NaYF4: Tm (1.75%) core. After growing an inert shell, a ten-fold increase of emission intensity was achieved. Combining the advantages of NIR-II wavelength and the higher-order nonlinear excitation, a promising facile excitation strategy was developed for the application of thulium-doped upconversion nanoparticles in nanoparticles imaging and cancer cell microscopic imaging.