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Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

Cyclic peptides (CPs) are emerging as promising drug candidates. Numerous natural CPs and their analogs are effective therapeutics against various diseases. Notably, many of them contain peptidyl cis-prolyl bonds. Due to the high rotational barrier of peptide bonds, conventional molecular dynamics simulations struggle to effectively sample the cis/trans-isomerization of peptide bonds. Previous studies have highlighted the high accuracy of the residue-specific force field (RSFF) and the high sampling efficiency of high-temperature molecular dynamics (high-T MD). Herein, we propose a protocol that combines high-T MD with RSFF2C and a recently developed reweighting method based on probability densities for accurate structure prediction of proline-containing CPs. Our method successfully predicted 19 out of 23 CPs with the backbone rmsd < 1.0 Å compared to X-ray structures. Furthermore, we performed high-T MD and density reweighting on the sunflower trypsin inhibitor (SFTI-1)/trypsin complex to demonstrate its applicability in studying CP-complexes containing cis-prolines. Our results show that the conformation of SFTI-1 in aqueous solution is consistent with its bound conformation, potentially facilitating its binding.

It is very challenging to accurately segment smoke images because smoke has some adverse vision characteristics, such as anomalous shapes, blurred edges, and translucency. Existing methods cannot fully focus on the texture details of anomalous shapes and blurred edges simultaneously. To solve these problems, a Dense Multi‐scale context and Asymmetric pooling Embedding Network (DMAENet) is proposed to model the smoke edge details and anomalous shapes for smoke segmentation. To capture the feature information from different scales, a Dense Multi‐scale Context Module (DMCM) is proposed to further enhance the feature representation capability of our network under the help of asymmetric convolutions. To efficiently extract features for long‐shaped objects, the authors use asymmetric pooling to propose an Asymmetric Pooling Enhancement Module (APEM). The vertical and horizontal pooling methods are responsible for enhancing features of irregular objects. Finally, a Feature Fusion Module (FFM) is designed, which accepts three inputs for improving performance. Low and high‐level features are fused by pixel‐wise summing, and then the summed feature maps are further enhanced in an attention manner. Experimental results on synthetic and real smoke datasets validate that all these modules can improve performance, and the proposed DMAENet obviously outperforms existing state‐of‐the‐art methods. To capture the feature information from different scales, a Dense Multi‐scale Context Module (DMCM) is proposed to further enhance the feature representation capability of our network under the help of asymmetric convolutions. To efficiently extract features for long‐shaped objects, the authors use asymmetric pooling to propose an Asymmetric Pooling Enhancement Module (APEM). To effectively fuse features, a Feature Fusion Module (FFM) is designed, which accepts three inputs for significantly improving performance.

Understanding how sleep affects the glymphatic system and human brain networks is crucial for elucidating the neurophysiological mechanism underpinning aging-related memory declines. We analyzed a multimodal dataset collected through magnetic resonance imaging (MRI) and polysomnographic recording from 72 older adults. A proxy of the glymphatic functioning was obtained from the Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. Structural and functional brain networks were constructed based on MRI data, and coupling between the two networks (SC-FC coupling) was also calculated. Correlation analyses revealed that DTI-ALPS was negatively correlated with sleep quality measures [e.g., Pittsburgh Sleep Quality Index (PSQI) and apnea-hypopnea index]. Regarding human brain networks, DTI-ALPS was associated with the strength of both functional connectivity (FC) and structural connectivity (SC) involving regions such as the middle temporal gyrus and parahippocampal gyrus, as well as with the SC-FC coupling of rich-club connections. Furthermore, we found that DTI-ALPS positively mediated the association between sleep quality and rich-club SC-FC coupling. The rich-club SC-FC coupling further mediated the association between DTI-ALPS and memory function in good sleepers but not in poor sleepers. The results suggest a disrupted glymphatic-brain relationship in poor sleepers, which underlies memory decline. Our findings add important evidence that sleep quality affects cognitive health through the underlying neural relationships and the interplay between the glymphatic system and multimodal brain networks.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitroand in vivotumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

BackgroundThe association between the TDRD6variants and human infertility remains unclear, as only one homozygous missense variant of TDRD6was found to be associated with oligoasthenoteratozoospermia (OAT).MethodsWhole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants of TDRD6in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients. Tdrd6-knockout mice were generated using the CRISPR–Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment.ResultsBi-allelic TDRD6variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using the Tdrd6-deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouring TDRD6variants. ScRNA-seq analysis of germ cells from a patient with TDRD6variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation.ConclusionOur findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship between TDRD6variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelic TDRD6variants, providing insights for potential clinical treatment strategies.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8and AK9were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

Pipeline leakage magnetic detection technology is an effective means to ensure the safe operation of pipelines. The key link in leakage detection technology is to determine the specific size of the defects according to the leakage signal. In the actual pipeline detection process, the defect shape is mostly complex and irregular, and the traditional rectangular defects are difficult to accurately characterize. In order to solve this problem, this article uses ellipsoidal defects as the research object to replace the complex defects in pipeline inspection, combines the ellipsoidal coordinate system, constructs the forward mathematical model of ellipsoidal defects through vector synthesis, and carries out mathematical analysis and calculation of the magnetic distribution law of the leakage signals in the pipeline in the three axes (axial, circumferential, and radial). In addition, a defect size inversion algorithm is constructed based on the constructed mathematical model, and systematic experiments are carried out. The results show that the smaller the length and the larger the width of the defects are more sensitive to the change of depth, and in this model, the errors of solving the radial component of the defects is 14.3% on average, and the errors of solving the axial component is 16.6% on average. The solution accuracy is improved compared to the traditional model. Under this orthogonal mathematical model, the distribution characteristics of the elliptical leakage magnetic field obtained are in good agreement with the inverse model, and the model is of practical significance for improving the quality of defect assessment.

Tomato cultivars with contrasting resistance to pathogens regulate root exudates differentially in response to Ralstonia solanacearumattacks. However, strategies using innate root exudates against infection remain unknown. This study analyzed the innate root exudates of two tomato cultivars and their functions in regulating R. solanacearuminfection. The innate root exudates differed between the two cultivars. Astaxanthin released from resistant plants inhibited colonization by R. solanacearumbut promoted motility, while neferine released from susceptible plants suppressed motility and colonization. The secretion of astaxanthin in resistant tomatoes promoted the growth of biocontrol fungi in soil and reduced the abundance of pathogenic fungi. Neferine secreted by the susceptible cultivar inhibited the relative abundance of the bacterial-biocontrol-related Bacillusgenus, indirectly reducing the soil’s immune capacity. This study revealed contrasting strategies using root exudates in resistant and susceptible tomato cultivars to cope with R. solanacearuminfection, providing a basis for breeding disease-resistant cultivars.

Semi-macrosegregation in continuously cast blooms and its associated carbide banding defects in hot-rolled bars were investigated to explore the characteristics, evolution, and control methods in high-carbon chromium bearing steel. It was found that the semi-macrosegregation exists only in the central equiaxed crystal zone of the blooms, and C, Cr solute elements inside show typical spot-like positive segregation. Carbide banding appears as white bright bands along the rolling direction, composed of high number density M3C carbide particles, with a significant effect on the mechanical properties of the rolled products. The hereditary evolution from semi-macrosegregation to carbide banding was established by means of banded segregation. Morphologically, normal semi-macrosegregation and carbide-typed semi-macrosegregation are formed based on whether Cr-rich primary carbides are generated. These two types of semi-macrosegregation evolved into two kinds of carbide banding respectively, that is, dark bands and bright bands defined according to the ability to reflect light under OM. To alleviate the carbide banding defect in rolling products of high-carbon chromium bearing steel, the morphology and area ratio of equiaxed crystals in continuous cast blooms should be modified. It is observed that the equiaxed crystal ratio in the bloom can be decreased from 62.5 % to 28 % by increasing liquid steel superheat and inhibiting superheat dissipation in the mold through casting practices. Additionally, the morphology of equiaxed crystals is related to the as-cast solidification structure, and when the equiaxed crystal ratio is large, the equiaxed crystals turn out to be coarser ones with only cellular primary dendrite; when the columnar crystals are longer, however, the equiaxed crystals appear as a dendrite structure with fine secondary dendrites. As a result, semi-macrosegregation was improved obviously with the fine dendrite structure splitting the local residual liquid phase, leading to the decrease of the maximum width of carbide banding from 268.41 μm to 73.72 μm, and the increase of mechanical properties in the rolled bar of high-carbon chromium bearing steel.

Sarcopenia is an age-related, progressive, and systemic skeletal muscle disorder that can lead to numerous adverse outcomes. Animal studies have shown that sesame can enhance skeletal muscle blood flow and improve physical performance. However, no studies have yet explored the association between sesame consumption and the incidence of sarcopenia in the general population.

Physical design flow through associated electronic design automation (EDA) tools plays an imperative role in the advanced integrated circuit design. Mostly, the parameters fed into physical design tools are mainly manually picked based on the domain knowledge of the experts. Nevertheless, owing to the ever-shrinking scaling down of technology nodes and the complexity of the design space spanned by combinations of the parameters, even coupled with the time-consuming simulation process, such manual explorations for parameter configurations of physical design tools have become extremely laborious. There exist a few works in the field of design flow parameter tuning. However, very limited prior arts explore the complex correlations among multiple quality-of-result (QoR) metrics of interest (e.g., delay, power, and area) and explicitly optimize these goals simultaneously. To overcome these weaknesses and seek effective parameter settings of physical design tools, in this article, we propose a multi-objective Bayesian optimization (BO) framework with a multi-task Gaussian model as the surrogate model. An information gain-based acquisition function is adopted to sequentially choose candidates for tool simulation to efficiently approximate the Pareto-optimal parameter configurations. The experimental results on three industrial benchmarks under the 7-nm technology node demonstrate the superiority of the proposed framework compared to the cutting-edge works.

In recent years, memristive crossbar-based neuromorphic computing systems (NCS) have provided a promising solution for neural network acceleration. However, stuck-at faults(SAFs) and process variations in memristor devices significantly degrade the computing accuracy of NCS. In this brief, we propose a unified robust network training framework for a memristive crossbar-based NCS, simultaneously taking the impacts of SAFs and variations into account. In order to incorporate SAFs and variations into the training process, an effective sampling strategy for SAF and an efficient variation injection technique based on the local reparameterization method are developed. Experimental results clearly demonstrate that the proposed training framework can boost the computation accuracy of NCS.

Compared with traditional convolutions, grouped convolutional neural networks are promising for both model performance and network parameters. However, existing models with the grouped convolution still have parameter redundancy. In this article, concerning the grouped convolution, we propose a sharing grouped convolution structure to reduce parameters. To efficiently eliminate parameter redundancy and improve model performance, we propose a Bayesian sharing framework to transfer the vanilla grouped convolution to be the sharing structure. Intragroup correlation and intergroup importance are introduced into the prior of the parameters. We handle the Maximum Type II likelihood estimation problem of the intragroup correlation and intergroup importance by a group LASSO-type algorithm. The prior mean of the sharing kernels is iteratively updated. Extensive experiments are conducted to demonstrate that on different grouped convolutional neural networks, the proposed sharing grouped convolution structure with the Bayesian sharing framework can reduce parameters and improve prediction accuracy. The proposed sharing framework can reduce parameters up to 64.17%. For ResNeXt-50 with the sharing grouped convolution on ImageNet dataset, network parameters can be reduced by 96.875% in all grouped convolutional layers, and accuracies are improved to 78.86% and 94.54% for top-1 and top-5, respectively.

Background: Bi-allelic variants in DNAH11have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. Methods: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11variants. Results: In this study, we identified seven novel variants in the DNAH11gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11gene variants.

The regulation of reactive oxygen species (ROS)-sensitive calcium (Ca2+) channels is of great significance in the treatment of tumors. Here, a simple ROS generation system is developed to activate ROS-sensitive ion channels for enhancing calcium-cascade-mediated tumor cell death under near-infrared (NIR) light irradiation. Upon irradiation with an 808 nm laser, a low-lethality amount of ROS facilitates plasmid transient potential receptor melastatin-2 (pTRPM2) gene release via cleavage of the Se–Se bonds, which contributed to enhancing the expression of TRPM2 in tumor cells. Meanwhile, ROS could potently activate TRPM2 for Ca2+influx to inhibit early autophagy and to further induce intracellular ROS production, which ultimately led to cell death in TRPM2 expressing tumor cells. Both in vitroand in vivodata show that nanoparticles have an excellent therapeutic effect on cancer upon NIR light. This work presents a simple modality based on NIR light to remotely control the ROS-sensitive ion channel for cancer therapy.

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Objective: To screen for differentially expressed serum microRNAs (miRNAs) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) compared with healthy participants and explore the mechanism of acupuncture in the treatment of IBS-D based on miRNAs.Methods: IBS-D patients that met the Rome III diagnostic criteria and age- and sex-matched healthy participants were enrolled between April 2017 and December 2017. Serum miRNA levels were initially determined using a TaqMan low-density array (TLDA) in pooled samples. Markedly altered miRNAs in IBS-D patients were subsequently validated using quantitative real-time polymerase chain reaction (qRT-PCR) on individual samples. All IBS-D patients accepted the acupuncture therapy for 6 weeks. The disease severity was assessed using the IBS symptom severity scale (IBS-SSS) questionnaire before and after treatment. After acupuncture, the patients’ serum was re-analyzed for altered expression of the miRNAs by qRT-PCR.Results: TLDA and qRT-PCR analysis revealed six upregulated miRNAs (miR-1305, miR-575, miR-149-5p, miR-190a-5p, miR-135a-5p, and miR-148a-3p; P< 0.05) and two downregulated miRNAs (miR-194-5p, miR-127-5p; P< 0.05) in IBS-D patients compared with healthy controls. Post acupuncture treatment, total IBS-SSS scores, severity of abdominal pain, duration of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits and disruption in quality of life decreased significantly (P< 0.001). Furthermore, the upregulated miR-148a-3p levels in IBS-D patients also decreased significantly after acupuncture (P< 0.05).Conclusions: The over-expression or reduced expression of several miRNAs may contribute to IBS-D pathogenesis. Acupuncture might downregulate miR-148a-3p through multiple pathways to alleviate or relieve IBS-D symptoms.Trial registration number: ChiCTR-IOR-17010860 (Chinese Clinical Trials Registry)

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats.Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting.Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining.Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

Timely and accurate diagnosis of lithium-ion battery faults is crucial for ensuring the safety of electric vehicles. While incremental capacity (IC)-based diagnostic methods are effective, they can only be employed under charging conditions. To address this issue, a fault diagnostic method based on phase plane analysis is proposed to extend the application to various operating conditions. In a phase plane, the battery voltage is plotted on the x-axis, while the differential in voltage is plotted on the y-axis. During charging, diagnostic vectors indicating the occurrence and type of faults are extracted from the trajectories in the phase plane. Under complex operating conditions, early faults can be detected based on the morphological and scale deviation of the trajectories. Experimental results have shown that the proposed method can effectively detect minor faults. The fault detection rate and detection accuracy rate under charging conditions are 96.25 % and 97.73 %, respectively, which are 17.5 % and 8.54 % higher than those of the IC-based diagnostic method. Furthermore, the fault detection rate and accuracy rate under UDDS (Urban Dynamometer Driving Schedule) are 91.76 % and 97.23 %, respectively. Additionally, the diagnostic speed of the proposed method is twice as fast as that of the IC-based method.

The SARS-CoV-2 pandemic has presented new challenges to food manufacturers. During the early phase of the pandemic, several large outbreaks of coronavirus disease 2019 (COVID-19) occurred in food manufacturing plants resulting in deaths and economic loss, with approximately 15% of personnel diagnosed as asymptomatic for COVID-19. Spread by asymptomatic and presymptomatic individuals has been implicated in large outbreaks of COVID-19. In March 2020, we assisted in implementation of environmental monitoring programs for SARS-CoV-2 in zones 3 and 4 of 116 food production facilities. All participating facilities had already implemented measures to prevent symptomatic personnel from coming to work. During the study period, from 17 March to 3 September 2020, 1.23% of the 22,643 environmental samples tested positive for SARS-CoV-2, suggesting that infected individuals were actively shedding virus. Virus contamination was commonly found on frequently touched surfaces such as doorknobs, handles, table surfaces, and sanitizer dispensers. Most processing plants managed to control their environmental contamination when they became aware of the positive findings. Comparisons of positive test results for plant personnel and environmental surfaces in one plant revealed a close correlation. Our work illustrates that environmental monitoring for SARS-CoV-2 can be used as a surrogate for identifying the presence of asymptomatic and presymptomatic personnel in workplaces and may aid in controlling infection spread.

To evaluate the effect and safety of acupuncture for the treatment of irritable bowel syndrome (IBS) through comparisons with those of polyethylene glycol (PEG) 4000 and pinaverium bromide.

Vanadium-based compounds are increasingly recognized to be promising for constructing safe and stable Zinc ion batteries (ZIBs). However, it is still a challenge to balance the mechanical flexibility and electrochemical performance for achieving flexible ZIBs (FZIBs). Herein, MXene and single-walled carbon nanotube(SWCNT)colloids are used respectively as conductive binders and structural reinforcements to achieve the desired flexibility and electrochemical properties. Systematic structural, morphological, and electrochemical evaluations show that the prepared freestanding cathode delivers decent rate capabilities, specific capacities (325.3 mAh g−1at 0.1 A g−1), and cycling stability (2000 cycles without obvious decay). Additionally, the cathode, benefitting from its interwoven frame network, demonstrates rapid electrochemical reaction kinetics. The quasi-reversibility of zinc ion storage in the electrode is further confirmed through a series of ex-situ characterization methods, providing evidence for its cycling stability. Most Importantly, as a result of the mechanical flexibility of the electrode, the fabricated FZIBs display a robust electrochemical stability in both a natural planar and bending states. Therefore, the strategy presented in this work is an effective approach for fabricating vanadium dioxide based FZIBs suitable for flexible electronics for many applications such as daily healthcare monitoring.

Because of its light weight, high strength, designable, composite materials are more and more widely used in the field of aerospace, especially in the field of general aviation. In this paper, the structural design and analysis of the composite wing (include wing beam, rib, skin, leading edge and trailing edge) of a four-seater electric aircraft were carried out. The finite element numerical analysis model of the composite wing was established, and the deformation and strain distribution of the composite wing under the limited load required by airworthiness regulations were calculated. Finally, the static test of the whole composite wing was carried out to verify the accuracy of the finite element results. The finite element analysis and testing results showed that the structural design of the composite wing of the electric aircraft meets the structural strength requirements specified in the airworthiness standard (part 23 of China civil aviation regulations: air-worthiness requirements for normal, practical, special effects and commuting aircraft: CCAR 23-R3)

A novel model-free iterative learning control algorithm is proposed in this paper to improve both the robustness against output disturbances and the tracking performance in steady-state. For model-free ILC, several methods have been investigated, such as the time-reversal error filtering, the Model-Free Inversion-based Iterative Control (MFIIC), and the Non-Linear Inversion-based Iterative Control (NLIIC). However, the time-reversal error filtering has a conservative learning rate. Other two methods, although with much faster error convergence, have either a high noise sensitivity or a non-optimized steady-state. To improve the performance and robustness of model-free ILC, we apply the time-reversal based ILC and recursively accelerate its error convergence using the online identified learning filter. The effectiveness of the proposed algorithm has been validated by a numerical simulation. The proposed approach not only improves the transient response of the MFIIC, but achieves lower tracking error in steady-state compared to that of the NLIIC.

In recent years, concerns have been raising about issues such as poor soft reduction effect and severe center segregation caused by uneven solidification during slab continuous casting. In view of this, a transient heat transfer-solidification model has been employed to reveal the effects of both water flux distribution uniformity and casting speed on uneven solidification morphology together with experimental observation. The industrial trials demonstrate severe segregation near the 1/8 width position of the slab castings. Nevertheless, both the macrosegregation ratio and distribution region markedly decrease by adjusting the soft reduction segments and/or casting speed to align the central solid fraction at the inlet and outlet of the segments with the optimized soft reduction zone. Given the uneven solidification of the slab castings, it's necessary to broaden the soft reduction zone. Additionally, the dimensionless perimeter L of semi-macro segregation was first introduced to characterize the morphological complexity. The optimized soft reduction parameters decrease the size and dimensionless perimeter L of semi-macro segregation, which is beneficial to the minimization of macro/semi-macro segregation.

IMPORTANCE: Caffeine is known to decrease vasodilation and have immunosuppressant effects, which may potentially decrease the risk of rosacea. However, the heat from coffee may be a trigger for rosacea flares. The relationship between the risk of rosacea and caffeine intake, including coffee consumption, is poorly understood. OBJECTIVE: To determine the association between the risk of incident rosacea and caffeine intake, including coffee consumption. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 82 737 women in the Nurses’ Health Study II (NHS II), a prospective cohort established in 1989, with follow-up conducted biennially between 1991 and 2005. All analysis took place between June 2017 and June 2018. EXPOSURES: Data on coffee, tea, soda, and chocolate consumption were collected every 4 years during follow-up. MAIN OUTCOMES AND MEASURES: Information on history of clinician-diagnosed rosacea and year of diagnosis was collected in 2005. RESULTS: A total of 82 737 women responded to the question regarding a diagnosis of rosacea in 2005 in NHS II and were included in the final analysis (mean [SD] age at study entry, 50.5 [4.6] years). During 1 120 051 person-years of follow-up, we identified 4945 incident cases of rosacea. After adjustment for other risk factors, we found an inverse association between increased caffeine intake and risk of rosacea (hazard ratio for the highest quintile of caffeine intake vs the lowest, 0.76; 95% CI, 0.69-0.84; P &lt; .001 for trend). A significant inverse association with risk of rosacea was also observed for caffeinated coffee consumption (HR, 0.77 for those who consumed ≥4 servings/d vs those who consumed &lt;1/mo; 95% CI, 0.69-0.87; P &lt; .001 for trend), but not for decaffeinated coffee (HR, 0.80; 95% CI, 0.56-1.14; P = .39 for trend). Further analyses found that increased caffeine intake from foods other than coffee (tea, soda, and chocolate) was not significantly associated with decreased risk of rosacea. CONCLUSIONS AND RELEVANCE: Increased caffeine intake from coffee was inversely associated with the risk of incident rosacea. Our findings do not support limiting caffeine intake as a means to prevent rosacea. Further studies are required to explain the mechanisms of action of these associations, to replicate our findings in other populations, and to explore the relationship of caffeine with different rosacea subtypes.

A precisely positioned sulfimide chiral center on-tether of a thio-ether tethered peptide determines the peptide secondary structure by chemoselective oxaziridine modification. This method provides a facile way to tune peptides’ secondary structures and biophysical properties.

A high-resolution displacement detection based on in-plane and out-of-plane moving gratings is discussed in this paper. To improve the detective resolution and stability, a model of a double metal/dielectric optical grating is established to investigate the tolerance of grating parameters. The zero-order optical diffraction efficiency of the grating is calculated by rigorous coupled-wavelength analysis, which depends on the grating parameters. The dependency relation curves are a cosine and pulse curve, respectively, for in-plane movement with the highest slope superior to 0.29%/nm and the highest resolution can reach to 0.01 nm, and for out-of-plane movement with the highest slope superior to 1.63%/nm and the optimum resolution can reach to 0.002 nm. These results indicate that the in-plane effect is feasible for a long-range and high-resolution displacement detection, and the out-of-plane effect is suitable for small-range and high-resolution displacement detection. Both kinds of effects provide a designed solution for the development of a high-resolution displacement sensor.

Background: Renal cell carcinoma (RCC) is a malignant tumour that may develop in the kidney. RCC is one of the most common kinds of tumours of this sort, and its most common pathological subtype is kidney renal clear cell carcinoma (KIRC). However, the aetiology and pathogenesis of RCC still need to be clarified. Exploring the internal mechanism of RCC contributes to diagnosing and treating this disease. Pyroptosis is a critical process related to cell death. Recent research has shown that pyroptosis is a critical factor in the initiation and progression of tumour formation. Thus far, researchers have progressively uncovered evidence of the regulatory influence that long noncoding RNAs (lncRNAs) have on pyroptosis. Methods: In this work, a comprehensive bioinformatics approach was used to produce a predictive model according to pyroptosis-interrelated lncRNAs for the purpose of predicting the overall survival and molecular immune specialties of patients diagnosed with KIRC. This model was verified from multiple perspectives. Results: First, we discovered pyroptosis-associated lncRNAs in KIRC patients using the TCGA database and a Sankey diagram. Then, we developed and validated a KIRC patient risk model based on pyroptosis-related lncRNAs. We demonstrated the grouping power of PLnRM through PCA and used PLnRM to assess the tumour immune microenvironment and response to immunotherapy. Immunological and molecular traits of diverse PLnRM subgroups were evaluated, as were clinical KIRC patient characteristics and predictive risk models. On this basis, a predictive nomogram was developed and analyzed, and novel PLnRM candidate compounds were identified. Finally, we investigated possible medications used by KIRC patients. Conclusions: The results demonstrate that the model generated has significant value for KIRC in clinical practice.

•Multiple sclerosis (MS) severely affects male sexual and reproductive health.•Sexual and reproductive dysfunction is often ignored in males with MS.•Psychological factors, genetic susceptibility, autoimmunity, chronic inflammation, and the use of drugs related to MS may potentially impact the sexual and reproductive health of males with MS.•Further studies are needed to give an in-depth insight into the specific mechanisms of male sexual and reproductive dysfunction associated with MS.

In this paper, the liquid phase separation and solidification process of the Al75Bi9Sn16 immiscible alloy were studied with calorimetric and resistivity methods to make the melt superheated treatment process. The impact of melt overheating treatment (MOT) on the phase constitution and solidification microstructures were investigated using X-Ray diffraction (XRD) and field emission scanning electron microscope (FESEM) to determine the structural sensitivity to the melt superheated degree, and find a new strategy for improving the forming ability of the core-shell structure of the Al75Bi9Sn16 alloy. The results show that: the liquid phase separation and precipitation of primary (Sn) phase occur in 1039K-880K and 460K-403K; the core-shell structure with Sn-Bi-rich core and Al-rich shell can be formed under conventional casting conditions; the melt overheating treatment (MOT) can promote the formation of core-shell structure by increasing solidification time t0 and decreasing the average solidification rate v.

As-cast Mg-3Er-xZn (x = 0, 0.5, 1 and 2 at.%) alloys were prepared by a cast ingot metallurgy process. The effect of Zn contents on the microstructure and phase constitution of the alloys was investigated by optical microscope (OM), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and transmission electronic microscope (TEM). The results revealed that the as-cast Mg-3Er alloy mainly consisted of α-Mg phase and MgEr eutectic phase. Typically, a small amounts of LPSO phase was precipitated at grain boundaries by adding 0.5 at.% Zn into Mg-3Er alloy. With the addition of 1 at.%Zn, the volume fraction of LPSO phase increased obviously. When the addition of Zn increased to 2 at.%, the volume fraction of LPSO phase decreases and Mg8ZnEr phase forms at grain boundaries. Tensile test indicated that Mg-3Er-1Zn alloy exhibits the excellent mechanical properties. The tensile strength, yield strength and elongation of Mg-3Er-1Zn alloy are 213 MPa, 187.6 MPa and 5.52%, increased by 38.8%, 60% and 3.19%, respectively, corresponding to the alloy without Zn addition. The excellent mechanical properties could be attributed to the introduction of Zn element in alloys, which leads to the strengthening of LPSO phase and grain refinement of α-Mg.

The emergence of drug-resistant bacteria severely challenges the antimicrobial agents and antibacterial strategy. Here, we demonstrate a novel, simple, and highly efficient combination therapy strategy by direct combinations of cationic conjugated polymers (CCPs) with polypeptide antibiotics against Gram-negative and Gram-positive bacteria based on a synergistic antibacterial effect. The combination therapy method enhances the antibacterial efficacy with a significantly reduced antibiotic dosage. Also, the highly efficient and synergistic killing of drug-resistant bacteria is realized. Using combinations of CCPs and antibiotics to show increased antibacterial activity, this strategy will provide a much wider scope of the discovery of efficient antibacterial systems than that of antibiotic–antibiotic combinations. The proposed combination therapy method provides a universal and powerful platform for the treatment of pathogens, in particular, the drug-resistant bacteria, and also opens a new way for the development of efficient antibacterial systems.

Graphene oxide has attracted widespread attention in the biomedical fields due to its excellent biocompatibility. Herein we investigated the layer-number dependent antibacterial and osteogenic behaviors of graphene oxide in biointerfaces. Graphene oxide with different layer numbers was deposited on the titanium surfaces by cathodal electrophoretic deposition with varied deposition voltages. The initial cell adhesion and spreading, cell proliferation, and osteogenic differentiation were observed from all the samples using rat bone mesenchymal stem cells. Both Gram-negative Escherichia coliand Gram-positive Staphylococcus aureuswere used to investigate the antibacterial effect of the modified titanium surfaces. Cocultures of human gingival fibroblasts (HGF) cells with Escherichia coliand Staphylococcus aureuswere conducted to simulate the conditions of the clinical practice. The results show that the titanium surfaces with graphene oxide exhibited excellent antibacterial and osteogenic effects. Increasing the layer-number of graphene oxide resulted in the augment of reactive oxygen species levels and the wrinkling, which led to the antibacterial and osteogenic effects, respectively. Compared to pure titanium surface in the cells–bacteria coculture process, the modified titanium surfaces with graphene oxide exhibited higher surface coverage percentage of cells.

Chromophore-assisted light inactivation (CALI) is a powerful tool for analyzing protein functions due to the high degree of spatial and temporal resolution. In this work, we demonstrate a CALI approach based on conjugated polymers (CPs)/DNA hybrid material for protein inactivation. The target protein is conjugated with single-stranded DNA in advance. Single-stranded DNA can form CPs/DNA hybrid material with cationic CPs via electrostatic and hydrophobic interactions. Through the formation of CPs/DNA hybrid material, the target protein that is conjugated with DNA is brought into close proximity to CPs. Under irradiation, CPs harvest light and generate reactive oxygen species (ROS), resulting in the inactivation of the adjacent target protein. This approach can efficiently inactivate any target protein which is conjugated with DNA and has good specificity and universality, providing a new strategy for studies of protein function and adjustment of protein activity.

We appreciate the insightful comments on our study.1Contrast-based imaging allows direct visualization of the glymphatic system and assessment of its function based on the pharmacokinetics of contrast agents. However, quantifications of glymphatic activity in individual fluid compartments may require other techniques.

From the perspective of surface modification of biomaterials, graphene is very promising because of its unique physical and chemical properties. Herein, we report direct in situ fabrication of graphene on nitinol (NiTi) shape memory alloy by chemical vapor deposition (CVD) and investigate both the growth mechanism as well as surface bioactivity of the modified alloy. Growth of the graphene layer is independent of Ni but is rather correlated with the formation of the TiC phase on the surface. Graphene nucleates and grows on this carbide layer during exposure to CH4. The graphene layer is observed to promote the osteogenesis differentiation of mesenchymal stem cells and surface bioactivity. The use of graphene as a bioactive layer is a viable approach to improving the surface properties of NiTi-based dental and orthopedic implants and components.

Metal matrix composites reinforced by graphene particles exhibit physical and mechanical property and are developed and qualified for use in aerospace structure, bioengineering, energy storage material and photoelectric device. In the present paper, graphene was fabricated by modify Hummers method, and then was surface modified by chemical plating copper. The graphene/Al composites were fabricated by powder metallurgic method. Morphology characterization of graphene and composites were detected by XRD and SEM,the fabrication parameters of composites were optimized by testing harness and density. The volume fraction of graphene particles was 3%, the density of composites was maximum of 96.5%. The hardness had a maximum of HB 42.6, and the hardness of graphene/Al composites increased by 33.5%.