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BackgroundExisting epidemiological data indicated a correlation between thyroid cancer (THCA) and the risk of secondary primary malignancies (SPMs). However, the correlation does not always imply causality.MethodsThe Mendelian randomization (MR) analyses were performed to investigate the causal relationships between THCA and SPMs based on international multicenter data. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The Cancer Genome Atlas (TCGA) was used to explore potential mechanisms shared by THCA and bladder cancer (BLCA).ResultsSummary datasets of genome-wide association studies (GWAS) on 30 types of cancers were obtained from the United Kingdom Biobank (UKB) and FinnGen database. Meta-analysis of the UKB and FinnGen results revealed that THCA was significantly positively correlated with BLCA (OR = 1.140; 95% CI, 1.072-1.212; P < 0.001). Four genes, including WNT3, FAM171A2, MLLT11, and ULBP1, were identified as key genes shared by both TCHA and BLCA. Correlation analysis indicated that THCA may increase the risk of secondary BLCA through augmentation of N2 neutrophil infiltration.ConclusionsThis study showed that THCA was causally related to BLCA. It is recommended to conduct more rigorous screenings for BLCA during the follow-up of THCA patients.

Transcatheter edge-to-edge repair (TEER) has been established as a safe and effective option for treating patients with severe symptomatic degenerative mitral regurgitation (MR) who are at prohibitive surgical risk. However, the significant cost presents a considerable disease burden in low-income countries. This case details the treatment of a high-surgical-risk patient with severe degenerative MR by using the GeminiOne (Peijia Medical) system—a novel Chinese TEER device.

Abstract Polymorphic structures of transition metal dichalcogenides (TMDs) host exotic electronic states, like charge density wave and superconductivity. However, the number of these structures is limited by crystal symmetries, which poses a challenge to achieving tailored lattices and properties both theoretically and experimentally. Here, we report a coloring-triangle (CT) latticed MoTe2 monolayer, termed CT-MoTe2, constructed by controllably introducing uniform and ordered mirror-twin-boundaries into a pristine monolayer via molecular beam epitaxy. Low-temperature scanning tunneling microscopy and spectroscopy (STM/STS) together with theoretical calculations reveal that the monolayer has an electronic Janus lattice, i.e., an energy-dependent atomic-lattice and a Te pseudo-sublattice, and shares the identical geometry with the Mo5Te8 layer. Dirac-like and flat electronic bands inherently existing in the CT lattice are identified by two broad and two prominent peaks in STS spectra, respectively, and verified with density-functional-theory calculations. Two types of intrinsic domain boundaries were observed, one of which maintains the electronic-Janus-lattice feature, implying potential applications as an energy-tunable electron-tunneling barrier in future functional devices.

The phylogenetic status of the family Nitidulidae and its sister group relationship remain controversial. Also, the status of the subfamily Meligethinae is not fully understood, and previous studies have been mainly based on morphology, molecular fragments, and biological habits, rather than the analysis of the complete mitochondrial genome. Up to now, there has been no complete mitochondrial genome report of Meligethinae. In this study, the complete mitochondrial genomes of Meligethinus tschungseni and Brassicogethes affinis (both from China) were provided, and they were compared with the existing complete mitochondrial genomes of Nitidulidae. The phylogenetic analysis among 20 species of Coleoptera was reconstructed via PhyloBayes analysis and Maximum likelihood (ML) analysis, respectively. The results showed that the full lengths of Meligethinus tschungseni and Brassicogethes affinis were 15,783 bp and 16,622 bp, and the AT contents were 77% and 76.7%, respectively. Each complete mitochondrial genome contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and a control region (A + T-rich region). All the PCGs begin with the standard start codon ATN (ATA, ATT, ATG, ATC). All the PCGs terminate with a complete terminal codon, TAA or TAG, except cox1, cox2, nad4, and nad5, which terminate with a single T. Furthermore, all the tRNAs have a typical clover-leaf secondary structure except trnS1, whose DHU arm is missing in both species. The two newly sequenced species have different numbers and lengths of tandem repeat regions in their control regions. Based on the genetic distance and Ka/Ks analysis, nad6 showed a higher variability and faster evolutionary rate. Based on the available complete mitochondrial genomes, the results showed that the four subfamilies (Nitidulinae, Meligethinae, Carpophilinae, Epuraeinae) of Nitidulidae formed a monophyletic group and further supported the sister group relationship of Nitidulidae + Kateretidae. In addition, the taxonomic status of Meligethinae and the sister group relationship between Meligethinae and Nitidulinae (the latter as currently circumscribed) were also preliminarily explored.

BackgroundMobile health (mHealth) apps are rapidly emerging technologies in China due to strictly controlled medical needs during the COVID-19 pandemic while continuing essential services for chronic diseases. However, there have been no large-scale, systematic efforts to evaluate relevant apps. ObjectiveWe aim to provide a landscape of mHealth apps in China by describing and comparing digital health concerns before and after the COVID-19 outbreak, including mHealth app data flow and user experience, and analyze the impact of COVID-19 on mHealth apps. MethodsWe conducted a semilongitudinal survey of 1593 mHealth apps to study the app data flow and clarify usage changes and influencing factors. We selected mHealth apps in app markets, web pages from the Baidu search engine, the 2018 top 100 hospitals with internet hospitals, and online shopping sites with apps that connect to smart devices. For user experience, we recruited residents from a community in southeastern China from October 2019 to November 2019 (before the outbreak) and from June 2020 to August 2020 (after the outbreak) comparing the attention of the population to apps. We also examined associations between app characteristics, functions, and outcomes at specific quantiles of distribution in download changes using quantile regression models. ResultsRehabilitation medical support was the top-ranked functionality, with a median 1.44 million downloads per app prepandemic and a median 2.74 million downloads per app postpandemic. Among the top 10 functions postpandemic, 4 were related to maternal and child health: pregnancy preparation (ranked second; fold change 4.13), women's health (ranked fifth; fold change 5.16), pregnancy (ranked sixth; fold change 5.78), and parenting (ranked tenth; fold change 4.03). Quantile regression models showed that rehabilitation (P75, P90), pregnancy preparation (P90), bodybuilding (P50, P90), and vaccination (P75) were positively associated with an increase in downloads after the outbreak. In the user experience survey, the attention given to health information (prepandemic: 249/375, 66.4%; postpandemic: 146/178, 82.0%; P=.006) steadily increased after the outbreak. ConclusionsmHealth apps are an effective health care approach gaining in popularity among the Chinese population following the COVID-19 outbreak. This research provides direction for subsequent mHealth app development and promotion in the postepidemic era, supporting medical model reformation in China as a reference, which may provide new avenues for designing and evaluating indirect public health interventions such as health education and health promotion.

Hunting behavior typically contains a sequential motor program, including search, chase, attack, and consumption. Here, the authors show that periaqueductal gray neuronal ensembles encode the sequential hunting motor program, which might provide a framework for decoding complex instinctive behaviors.

Summary: Background: As aortic aneurysms (AAs) enlarge, they can become life-threatening if left undiagnosed or neglected. At present, there is a lack of radical treatments for preventing disease progression. Therefore, we aimed to identify effective drug targets that slow the progression of AAs. Methods: A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets which are associated with AAs. Summary statistics for AAs were obtained from two datasets: the UK Biobank (2228 cases and 408,565 controls) and the FinnGen study (3658 cases and 244,907 controls). Cis-expression quantitative trait loci (cis-eQTL) for druggable genes were retrieved from the eQTLGen Consortium and used as genetic instrumental variables. Colocalization analysis was performed to determine the probability that single nucleotide polymorphisms (SNPs) associated with AAs and eQTL shared causal genetic variants. Findings: Four drug targets (BTN3A1, FASN, PLAU, and PSMA4) showed significant MR results in two independent datasets. Proteasome 20S subunit alpha 4 (PSMA4) and plasminogen activator, urokinase (PLAU) in particular, were found to have strong evidence for colocalization with AAs, and abdominal aortic aneurysm in particular. Additionally, except for the association between PSMA4 and intracranial aneurysms, no association between genetically proxied inhibition of PLAU and PSMA4 was detected in increasing the risk of other cardiometabolic risks and diseases. Interpretation: This study supports that drug-targeting PLAU and PSMA4 inhibition may reduce the risk of AAs. Funding: This work was supported by National Key R&D Program of China (NO. 2017YFC0909400), Nature Science Foundation of China (No. 91839302, 81790624), Project supported by Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01), and Tongji Hospital Clinical Research Flagship Program (no. 2019CR207).

ObjectiveALPK3 is associated with a recessive form of pediatric cardiomyopathy accompanied by musculoskeletal and craniofacial abnormalities. Heterozygous truncating variants in this gene (ALPK3tv) have recently been confirmed as a cause of autosomal dominant hypertrophic cardiomyopathy (HCM). Whether ALPK3 is also implicated in HCM in East Asia and the effect of missense variants in ALPK3 on HCM remains unresolved.MethodsWe compared the frequency of rare deleterious variants in ALPK3 in a study cohort comprised of 793 HCM cases of East Asian descent to that in the controls subset of Genome Aggregation Database (gnomAD). Gene burden test was used to assess this association. The involvement of these variants in HCM was further validated by independent cohort. The clinical characteristics and prognoses of these carriers were compared with sarcomere-positive and negative patients.ResultsRare deleterious variants in ALPK3 were significantly enriched in HCM compared with gnomAD controls (truncating: 4/793 vs. 4/4523, P = 0.02; missense: 25/793 vs. 46/4523, P = 2.56e-5). Replication in an independent cohort provided more supporting evidence. Further comparisons revealed that ALPK3 carriers displayed more severe hypertrophy in interventricular septum (IVS) and apex, as well as greater maximal left ventricular wall thickness, relative to sarcomere negatives.ConclusionHeterozygous rare variants in ALPK3, both missense and truncating variants, are associated with HCM in East Asians.

This study focused on comprehensively analyzing the construction, mechanism, and design theory of the Thick Rubber Bearing–Disk Spring Bearing (TNRB-DSB) system, with the aim of evaluating its isolation effect. Mechanical tests were conducted to examine the dynamic characteristics of large-span isolated structures equipped with TNRB-DSBs, and laminated rubber bearings (LRBs), as well as the dynamic responses of non-isolated structures and large-span horizontal isolated structures equipped with natural rubber bearings (NRBs) and LRBs, under various seismic excitations. Finite element software was utilized to compare the behaviors of these structures. The study revealed that the large-span isolated structure equipped with TNRB-DSBs and LRBs had a vertical natural vibration period 1.23 times as long as that of the isolated structure with NRBs and LRBs, and 4.27 times as long as that of the non-isolated structure. The TNRB-DSB system demonstrated good vertical and horizontal isolation capabilities, which compensated for the isolation limitations of other rubber bearings to some extent.

Wood is one of the most abundant biomaterials on Earth, which has been used for centuries in construction applications including furniture, roofing, flooring, and cabinetry. However, wood chips—which are a low-quality and plentiful waste byproduct of lumber milling, woodworking, and shipping operations—have low economic value and complicated disposal methods. In this paper, we propose a strategy for wood chip reuse through the fabrication of bio-based building insulation foam. Through a high-temperature chemical treatment delignification process, we introduced additional small pores within the wood chips, effectively lowering their thermal conductivity, and used them in combination with a binding agent to produce a porous insulation foam. The porous insulation foam achieved a low thermal conductivity of 0.038 W/(m·K) and a high compressive strength of 1.1 MPa (70% strain). These characteristics demonstrate that wood waste can be repurposed into an effective building material, addressing challenges in both waste management and sustainable construction.

Transparent wood composites are promising engineered materials for green energy-efficient building. Here, authors demonstrate novel aesthetic wood with integrated functions of optical transparency, UV-blocking, thermal insulation, and mechanical strength for this sustainable application.

Abstract Powder to bulk processes, such as additive manufacturing and metal injection molding (MIM), have enabled great potential for complex metal designing and manufacturing. However, additive manufacturing process normally introduces a high residue stress and textures due to the locally intense temperature. MIM is an excellent batch manufacturing process; nevertheless, it is not suitable for rapid screening and development of new metal compositions and structures due to the slow sintering process. Herein, an ultrafast high‐temperature sintering (UHS) process is reported that enables the rapid synthesis and sintering of bulk metals/alloys and intermetallic compounds. In this process, elemental powders are mixed and pressed into pellets, followed by UHS sintering in just seconds at a temperature between 1000 and 3000 °C. Three representative compositions, including pure metals, intermetallics, and multielement alloys, are demonstrated with a broad range of melting points. The UHS process for metal sintering is nonmaterials specific, in addition to being extremely rapid, which make it suitable for materials discovery. Furthermore, the sintering method does not apply pressure to the samples, making it compatible with 3D printing and other additive manufacturing processes of complex structures. This rapid sintering technique will greatly facilitate the development and manufacturing of metals and alloys.

Thin films of several microns in thickness are ubiquitously used in packaging, electronics, and acoustic sensors. Here the authors demonstrate an ultrathin wood film with an aligned and laminal structure and acoustic properties which allows application of the film as diaphragm for an audio speaker.

Background: Monochromatic blue light (MBL), with a wavelength between 400–490 nm, can regulate non-image-forming (NIF) functions of light in the central nervous system. The suprachiasmatic nucleus (SCN) in the brain is involved in the arousal-promoting response to blue light in mice. Animal and human studies showed that the responsiveness of the brain to visual stimuli is partly preserved under general anesthesia. Therefore, this study aimed to investigate whether MBL promotes arousal from sevoflurane anesthesia via activation of the SCN in mice.Methods: The induction and emergence time of sevoflurane anesthesia under MBL (460 nm and 800 lux) exposure was measured. Cortical electroencephalograms (EEGs) were recorded and the burst-suppression ratio (BSR) was calculated under MBL during sevoflurane anesthesia. The EEGs and local field potential (LFP) recordings with or without locally electrolytic ablated bilateral SCN were used to further explore the role of SCN in the arousal-promoting effect of MBL under sevoflurane anesthesia. Immunofluorescent staining of c-Fos was conducted to reveal the possible downstream mechanism of SCN activation.Results: Unlike the lack of effect on the induction time, MBL shortened the emergence time and the EEG recordings showed cortical arousal during the recovery period. MBL resulted in a significant decrease in BSR and a marked increase in EEG power at all frequency bands except for the spindle band during 2.5% sevoflurane anesthesia. MBL exposure under sevoflurane anesthesia enhances the neuronal activity of the SCN. These responses to MBL were abolished in SCN lesioned (SCNx) mice. MBL evoked a high level of c-Fos expression in the prefrontal cortex (PFC) and lateral hypothalamus (LH) compared to polychromatic white light (PWL) under sevoflurane anesthesia, while it exerted no effect on c-Fos expression in the ventrolateral preoptic area (VLPO) and locus coeruleus (LC) c-Fos expression.Conclusions: MBL promotes behavioral and electroencephalographic arousal from sevoflurane anesthesia via the activation of the SCN and its associated downstream wake-related nuclei. The clinical implications of this study warrant further study.

At the molecular level, biological activities involve the transport of ions in a system. Here the authors demonstrate an ‘electron battery’ by inverting the configuration of a traditional Li-ion battery to generate an ionic current to interact with a biosystem for potential biomedical applications.

Purpose: Currently, of the two most common staging systems of pancreatic neuroendocrine tumors (pNETs) one is from the European Neuroendocrine Tumor Society (ENETS) and the other is from the American Joint Committee on Cancer (AJCC). However, there are imperfections in both these staging systems.Patients and methods: Patients were selected retrospectively from the Surveillance Epidemiology and End Results (SEER) database (2004 to 2013). The effect of age on the hazard ratio (HR) was evaluated using restricted cubic splines. The discriminatory power of the staging systems was determined using the concordance index (C-index).Results: A total of 3,034 patients with pNETs were included in the final analyses. The risk of death increased slowly along with age for patients under 60 years of age, but the risk of death rose sharply for those over 60 years of age, forming a mirrored L-shaped survival curve. In the current AJCC tumor-node-metastasis (TNM) staging system, no statistical significance was observed between stages IA and IB (p = 0.105). Patients with stage IIB even had longer OS than patients with IIA, although there was no statistical significance (p = 0.574). The proportion of stage III patients was small (2.7%). In the proposed aTNM staging system, significant survival differences could be observed among stage I, IIA, and IIB (p < 0.001) and the proportion of stage III rose from 2.7 to 25.7%.Conclusion: Our findings suggest that age has a critical influence on the survival of patients with pNETs. Age should be considered as a factor in future staging systems of pNETs.

Purpose: Consensus-based clinical guidelines recommend that simple cholecystectomy (SC) is adequate for T1a gallbladder adenocarcinoma (GBA), but extended cholecystectomy (EC), SC plus lymphatic dissection, should be considered for T1b and more advanced GBA. Whether lymphatic dissection is necessary for the treatment of T1b GBA remains controversial. This study attempts to better define the current criteria for local treatment of T1b GBA, by examining the relationship between lymph node (LN) metastasis and tumor size in such patients.Patients and methods: Clinical data from patients with T1b GBA receiving curative surgical treatment between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Baseline characteristics for the entire cohort were described, and overall survival (OS) and cancer-specific survival (CSS) were analyzed with the Kaplan–Meier method.Results: In total, 277 patients were enrolled for further analysis; 127 underwent lymphadenectomy. Among them, 23 patients had tumors

Nanoparticles of non-noble metals are useful for many applications but can be prone to sintering or surface oxidation. Here, the authors use a rapid heating-cooling approach to synthesize uniformly distributed nanoparticles in a reduced graphene oxide matrix, and test them as switchable energetic materials.

Carbonaceous materials, such as graphite, carbon nanotubes (CNTs), and graphene, are in high demand for a broad range of applications, including batteries, capacitors, and composite materials. Studies on the transformation between different types of carbon, especially from abundant and low-cost carbon to high-end carbon allotropes, have received surging interest. Here, we report that, without a catalyst or an external carbon source, biomass-derived amorphous carbon and defective reduced graphene oxide (RGO) can be quickly transformed into CNTs in highly confined spaces by high temperature Joule heating. Combined with experimental measurements and molecular dynamics simulations, we propose that Joule heating induces a high local temperature at defect sites due to the corresponding high local resistance. The resultant temperature gradient in amorphous carbon or RGO drives the migration of carbon atoms and promotes the growth of CNTs without using a catalyst or external carbon source. Our findings on the growth of CNTs in confined spaces by fast high temperature Joule heating shed light on the controlled transition between different carbon allotropes, which can be extended to the growth of other high aspect ratio nanomaterials.