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Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

The female characters with a 46, XY karyotype, historically termed Swyer syndrome, are commonly divided into complete and partial gonadal dysgenesis. The former is completely made up of the 46, XY chromosome, while the latter results from 45, X/46, XY mosaicism. Both of them are sex chromosome disorders and are typically characterized by delayed puberty and primary amenorrhea due to disruption of the embryonic gonads into testes. In this report, we described a young female with mos 45, X [2]/46, X, psu idic (Y) (q11.2) [48] by karyotyping. Further copy number variation sequencing (CNV-seq) and fluorescent in situ hybridization (FISH) verified her chromosome alteration. The following gonadectomy and hormone replacement therapy were carried out, and the menstrual cycle recovered along with the development of bilateral breasts and uteruses. Herein, we aim to provide clinical management strategies for the patient with Swyer syndrome in clinical practice.

Objective: The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy. Methods: Chinese patients with TNBC who received chemotherapy between May 1, 2008 and March 31, 2020 were retrospectively analyzed with a customized 3D-HRD panel. HRD positivity was defined by an HRD score ≥ 30 or deleterious BRCA1/2 mutation. A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort (NCT01150513) and a metastatic cohort, and 189 patients with available clinical and tumor sequencing data were included. Results: In the entire cohort, 49.2% (93/189) of patients were identified as HRD positive (40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of ≥ 30). In the first-line metastatic setting, platinum therapy was associated with longer median progression-free survival (mPFS) than platinum-free therapy [9.1 vs. 3.0 months; hazard ratio (HR), 0.43; 95% confidence interval 0.22–0.84; P = 0.01]. Among HRD-positive patients, the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy (13.6 vs. 2.0 months; HR, 0.11; P = 0.001). Among patients administered a platinum-free regimen, HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients (P = 0.02; treatment-biomarker P-interaction = 0.001). Similar results were observed in the BRCA1/2-intact subset. In the adjuvant setting, HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy (P = 0.05, P-interaction = 0.02). Conclusions: HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

The personalized pattern generation method based on 2D body-measuring technology has considerable application potential in clothing e-commerce, remote clothing customization, clothing production, and other aspects. By inputting the front and side body images, this study proposed a new method of generating personalized patterns automatically. The silhouettes could be extracted from the body images to estimate body sizes and design style. The basic rules between the patterns and the body sizes were analysed, and the rules of the general pattern generation were established through a knowledge-based combination of the basic pattern and the style parameters. The sizes extracted from images were compared with the manually measured values, and the errors of these sizes were analysed. Sample pants were made and tried on with the automatic pattern generation system, and the experiments showed that the sample pants have a good fit at some key landmarks. As a result, this system can automatically generate personalized patterns and style designs based on 2D human body images, to improve garment fit and accelerate clothing customization.

In this paper, an interior penalty virtual element method (IPVEM) is developed for solving the biharmonic problem on polygonal meshes. By modifying the existing H 2 H^2 -conforming virtual element, an H 1 H^1 -nonconforming virtual element is obtained with the same degrees of freedom as the usual H 1 H^1 -conforming virtual element, such that it locally has H 2 H^2 -regularity on each polygon in meshes. To enforce the C 1 C^1 continuity of the solution, an interior penalty formulation is adopted. Hence, this new numerical scheme can be regarded as a combination of the virtual element space and discontinuous Galerkin scheme. Compared with the existing methods, this approach has some advantages in reducing the degree of freedom and capability of handling hanging nodes. The well-posedness and optimal convergence of the IPVEM are proven in a mesh-dependent norm. We also derive a sharp estimate of the condition number of the linear system associated with IPVEM. Some numerical results are presented to verify the optimal convergence of the IPVEM and the sharp estimate of the condition number of the discrete problem. Besides, in the numerical test, the IPVEM has a good performance in computational accuracy by contrast with the other VEMs solving the biharmonic problem.

Let L be a commutative unital quantale. For every L-fuzzy relation E on a nonempty set X, we define an upper rough approximation operator on LX, which is a fuzzy extension of the classical Pawlak upper rough approximation operator. We show that this operator has close relation with the subsethood operator on X. Conversely, by an L-fuzzy closure operator on X, we can easily get an L-fuzzy relation. We show that this relation can be characterized by more smooth ways. Without the help of the lower approximation operator, L-fuzzy rough sets can still be studied by means of constructive and axiomatic approaches, and L-fuzzy similarities and L-fuzzy closure operators are one-to-one corresponding. We also show that, the L-topology induced by the upper rough approximation operator is stratified and Alexandrov.

Voltage-gated K+ (Kv) channels play a role in the cellular processes of various cancer cells, including lung cancer cells. We previously identified and reported a salivary protein from the Xenopsylla cheopis, FS48, which exhibited inhibitory activity against Kv1.1-1.3 channels when assayed in HEK 293T cells. However, whether FS48 has an inhibitory effect on cancer cells expressing Kv channels is unclear. The present study aims to reveal the effects of FS48 on the Kv channels and the NCI-H460 human lung cancer cells through patch clamp, MTT, wound healing, transwell, gelatinase zymography, qRT-PCR and WB assays. The results demonstrated that FS48 can be effective in suppressing the Kv currents, migration, and invasion of NCI-H460 cells in a dose-dependent manner, despite the failure to inhibit the proliferation. Moreover, the expression of Kv1.1 and Kv1.3 mRNA and protein were found to be significantly reduced. Finally, FS48 decreases the mRNA level of MMP-9 while increasing TIMP-1 mRNA level. The present study highlights for the first time that blood-sucking arthropod saliva-derived protein can inhibit the physiological activities of tumour cells via the Kv channels. Furthermore, FS48 can be taken as a hit compound against the tumour cells expressing Kv channels.

Aim. Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods. Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results. DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion. DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Taihang chickens are a domestic breed distributed throughout Hebei province in the Taihang Mountains of China and are characterized by their high meat and egg quality. However, the relatively limited egg production by this breed constrains their more widespread commercial utilization. The follicle selection process is closely linked to oocyte development and ovulation, making it a key determinant of laying performance and fecundity in hens. To understand the biological basis for such follicle selection and to identify the associated regulatory pathways, we conducted a genome-wide analysis of long noncoding RNAs (lncRNAs) and mRNAs from the pre-hierarchical follicles and hierarchical follicles of Taihang laying hens. We identified 81 lncRNAs and 528 mRNAs that were differentially expressed during follicle selection, and integrated network analyses suggested that these RNAs were associated with the cell cycle, focal adhesion, oocyte meiosis, peroxisome proliferator-activated receptor signaling, and steroid hormone biosynthesis pathways. The identified lncRNAs were also predicted to influence a series of target genes in cis and trans, suggesting that they may be important regulators of ovarian follicular development. Overall, the present analysis of lncRNA and mRNA expression patterns associated with ovarian follicle development offers a new foundation for future studies of reproductive physiology in Taihang chickens, highlighting new opportunities to improve the laying performance of this important domestic breed.

The Janus monolayer 2H-GdXY (X, Y = Cl, Br, I) combines both intrinsic valley splitting and strong Dzyaloshinskii–Moriya interaction (DMI), which can be greatly tuned by biaxial strain to obtain a skyrmions with expected size.

An electron donor–acceptor complex strategy that enabled photoactivation of aryl chlorides has been reported with the toluene anion or tBuOK as the electron donor.

One-pot synthesis of 4-(imidazol-1-yl)indole derivatives through sequential dearomatization and Ag-catalyzed cyclization/Cs2CO3-mediated addition/aromatization reaction.

A novel gold-catalyzed cycloisomerization/[2 + 1]cycloaddition/rearrangement of enyne-amides and sulfur ylides is reported. This strategy enables rapid and efficient construction of a series of α-pyrone derivatives.

Atherosclerosis has become a leading public health problem. Previous studies suggest that enhanced muscle strength and muscle-derived cytokines (myokines) are linked with atherosclerosis. However, no previous prospective study has examined the relationship between grip strength (GS) and carotid atherosclerosis (CAS) in middle-aged and older adults. We therefore designed a cohort study to investigate the association between GS and the incidence of CAS in a population aged 45 years and over.The cohort study (n = 1258; follow-up range: 1-6 years, median: 4.0 years, age range: 45-85 years) was performed from 2013 to 2019 in Tianjin, China. CAS was measured using a carotid artery B-mode ultrasound system and defined by increased carotid intima-media thickness and plaques. GS was measured using a handheld digital dynamometer. Adjusted Cox proportional hazards regression models were used to assess the association between quartiles of GS and CAS.The incidence of CAS was 122 cases per 1000 person-years. In the final multivariable models, the adjusted hazard ratios (HRs) [95 % confidence interval (CI)] for CAS across quartiles of weight-adjusted GS (Q1-Q4) were as follows: 1.00 (reference), 0.82 (0.63, 1.06), 0.92 (0.71, 1.19), 0.69 (0.52, 0.91) and the HRs (95 % CI) across quartiles of GS (Q1-Q4) were as follows: 1.00 (reference), 1.06 (0.83, 1.36), 0.78 (0.59, 1.02), 0.76 (0.58, 0.995). For one unit and one standard deviation (SD) increase in weight-adjusted GS, the adjusted HRs (95 % CI) of CAS were 0.16 (0.05, 0.52) and 0.82 (0.72, 0.93), respectively. For one unit and one SD increase in GS, the adjusted HRs (95 % CI) of CAS were 0.98 (0.96, 0.995), and 0.47 (0.26, 0.83), respectively.Higher GS was associated with a lower incidence of carotid atherosclerosis in middle-aged and older adults. Further studies are required to clarify the causality.

A photocatalytic dehydration method was developed to efficiently convert benzyl alcohols to the corresponding amides.

Delaying rice starch (RS) retrogradation can improve the quality parameters of rice-based starchy foods during storage. Modification of insoluble dietary fibre has always been used in the starchy food industry. Compared with vegetal insoluble dietary fibre, bacterial cellulose (BC) has many advantages such as high purity, smaller particle size, and elevated water absorption capacity. In the present work, BC was modified by high-pressure homogenisation (MBC) with different pressure levels (0, 50, 80, 120, and 160 MPa) to investigate the effect of MBC on RS retrogradation. Results showed that high-pressure homogenisation could decrease the particle size of BC. MBC addition to RS decreased paste breakdown and setback, thus suggesting that MBC might be a good candidate for increasing the stability of RS paste, and inhibiting its short-term retrogradation. The thermal properties and X-ray diffraction patterns of RS indicated that supplementing MBC could decrease the gelatinised enthalpy and relative crystallinity of RS paste during storage. Results also indicated that MBC could provide an opportunity to restrain RS retrogradation, and might be suitable for designing fibre-enriched products.

To produce high-quality, real-world evidence for oncologists by collating scattered gynaecologic oncology (GO) medical records in China.Retrospective study.The National Union of Real-world Gynaecological Oncology Research and Patient Management Platform (NUWA platform).Patient-centred data pool.The NUWA platform integrated inpatient/outpatient clinical, gene and follow-up data. Data of 11 456 patients with ovarian cancer (OC) were collected and processed using 91 345 electronic medical records. Structured and unstructured data were de-identified and re-collated into a patient-centred data pool using a predefined GO data model by technology-aided abstraction.Recent treatment pattern shifts towards precision medicine for OC in China.Thirteen first-tier hospitals across China participated in the NUWA platform up to 7 December 2021. In total, 3504 (30.59%) patients were followed up by a stand-alone patient management centre. The percentage of patients undergoing breast cancer gene (BRCA) mutation tests increased by approximately six-fold between 2017 and 2018. A similar trend was observed in the administration rate of poly(ADP-ribose) polymerase inhibitors as first-line treatment and second-line treatment after September 2018, when olaparib was approved for clinical use in China.The NUWA platform has great potential to facilitate clinical studies and support drug development, regulatory reviews and healthcare decision-making.

Salient but task-irrelevant distractors interfere less with visual search when they appear in a display region where distractors have appeared more frequently in the past (‘distractor-location probability cueing’). This effect could reflect the (re-)distribution of a global, limited attentional ‘inhibition resource’. Accordingly, changing the frequency of distractor appearance in one display region should also affect the magnitude of interference generated by distractors in a different region. Alternatively, distractor-location learning may reflect a local response (e.g., ‘habituation’) to distractors occurring at a particular location. In this case, the local distractor frequency in one display region should not affect distractor interference in a different region. To decide between these alternatives, we conducted three experiments in which participants searched for an orientation-defined target while ignoring a more salient orientation distractor that occurred more often in one vs. another display region. Experiment 1 varied the ratio of distractors appearing in the frequent vs. rare regions (60/40–90/10), with a fixed global distractor frequency. The results revealed the cueing effect to increase with increasing probability ratio. In Experiments 2 and 3, one (‘test’) region was assigned the same local distractor frequency as in one of the conditions of Experiment 1, but a different frequency in the other region – dissociating local from global distractor frequency. Together, the three experiments showed that distractor interference in the test region was not significantly influenced by the frequency in the other region, consistent with purely local learning. We discuss the implications for theories of statistical distractor-location learning.Public Significance StatementWe are frequently distracted by salient visual stimuli which are irrelevant to the task at hand. Previous studies have shown that ‘knowledge’ of the location(s) where a distractor is most likely to occur helps the observer to mitigate distraction. In this study we compared different theories of how the frequency and spatial distribution of distractor occurrence in different locations could influence the ability to avoid distraction. The results favored a local learning account: the ability to avoid distraction by distractors occuring in a particular spatial region is primarily influenced by how often distractors have occurred in that region.

The global infectious disease COVID-19 is caused by SARS-CoV-2, a new member of the Coronaviridae family. Though presented as a novel disease that primarily affects the respiratory system, multi-organ involvement has been well-noticed and documented since the beginning of the pandemic. When performed properly with adequate safety measures, autopsy provides the most valuable information to decipher the pathogenesis of this novel disease, therefore providing a basis for clinical management. In addition to reviewing the macroscopic changes in organs and tissues involved in COVID-19, the relevant microscopic alterations and possible pathogenesis are also discussed.

The baffle design resisting dry granular flow is still impeded by the effect of the particle size distribution coupled with the influence of Froude characteristics on baffle performance – for example, the deceleration process and run-up process. Based on discrete-element method simulation, this study investigated the baffle deceleration and granular flow run-up. Baffle deceleration is controlled by the change of particle contact behaviour behind the baffle slits and is more sensitive to the particle size than the Froude characteristics of granular flow. Although the granular flow run-up height is also affected by the debris–slit interaction, it is mainly dominated by the flow climbing along the baffle, which is more sensitive to the Froude characteristics and stress-transfer mechanism. Bidisperse granular flow has more complex interaction with the baffle compared with monodisperse flow. The effect of material inhomogeneity on baffle performance depends on the particle content. For baffle design, the first array can be considered as a reference. The estimation of the baffle deceleration potential and height with consideration to unsteady dynamics and material inhomogeneity is also presented in this paper.

The genus Meganola Dyar, 1898 was described from North America with type species, Meganola conspicua Dyar, 1898 by monotype. Poole (1898) assigned to it all taxa of Roeselia Hübner (which is currently a synonym of Nola Leach), except those of Sarbena Walker and Proneca Swinhoe. Meganola is widely distributed in the Old and New Worlds (Hacker et al., 2012; László et al., 2015).

为实现水下滑翔机低功耗、长航程的目标, 提高水下滑翔机升阻比是切实可行的手段之一。采用翼身融合布局设计了一款翼身融合水下滑翔机(blended-wing-body underwater glider, BWBUG), 利用NURBS样条曲线构建BWBUG的精细化参数模型, 以升阻比为优化目标, 运用组合优化算法, 开展BWBUG的多参数优化研究, 建立优化算法与黏流软件接口, 优化过程中直接耦合调用水动力计算, 大大提高了优化效率。结果表明, 优化后的BWBUG模型升力系数提升了0.58%, 阻力系数降低了10.22%, 升阻比提升12.01%, 水动力综合性能提升11.99%。文中所建立的优化方法对提高水下航行器构型优化具有重要的指导意义。

This study was to investigate whether the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) and T-helper 17 (Th17)/regulatory T (Treg) balance are associated with chronic apical periodontitis (CAP) relived by 0.1% nano-silver. CAP rat models were established by opening the first molars of the right and left mandible and exposing the pulp cavity to the oral cavity. CAP model was verified by cone-beam computed tomography, X-ray digital radiovisiography, and hematoxylin-eosin (H and E) staining. The rats were randomly divided into the sham, Ca(OH)

Polymorphisms have been identified to predispose to primary gouty arthritis (GA) and hyperuricemia (HUA). Here, we accessed the five polymorphisms of rs10754558, rs35829419, rs3738448, rs3806268, and rs7525979 in NLRP3 on GA and HUA susceptibility. We collected 1198 samples (314 GA, 377 HUA, and 507 controls) for this case-control study. Our data detected that the rs3806268 (GA vs. AA: OR = 0.65 , p = 0.012 ) was significantly associated with the susceptibility to GA. The rs3738448 (TT vs. GG: OR = 2.05 , p = 0.024 ) and rs7525979 (TT vs. CC: OR = 1.96 , p = 0.037 ) were significantly associated with the susceptibility to HUA. The rs3806268 AG genotype presented decreased risk of GA among the hypertension ( OR = 0.54 , p = 0.0093 ), smoking ( OR = 0.59 , p = 0.018 ), and no obesity ( OR = 0.60 , p = 0.0097 ) subjects compared to the GG genotype group. The rs3738448 TT genotype demonstrated increased risk of HUA among the hypertension ( OR = 4.10 , p = 0.0056 ) and no drinking population ( OR = 3.56 , p = 0.016 ) compared to the GG genotype group. The rs7525979 TT genotype demonstrated increased risk of HUA among the hypertension ( OR = 4.01 , p = 0.0064 ) and no drinking population ( OR = 3.24 , p = 0.034 ) compared to the CC genotype group. Furthermore, a significant haplotype effect of rs10754558/C-rs35829419/C-rs3738448/G-rs3806268/A-rs7525979/C was found ( OR = 1.60 , p = 0.0046 ) compared with GCGAC haplotype. Bioinformatics analyses indicated that rs3738448, rs3806268, and rs7525979 might influence the gene regulation, while the T-allele of rs3738448 increased the stability of NLRP3-mRNA. Collectively, our case-control study confirms NLRP3 polymorphisms might participate in regulating immune and inflammation responses in GA and HUA.

To improve the combination of graphite and copper, the friction and wear of a graphite/copper composite with a high content of graphite (50 wt %), copper-coated graphite were used to modify it. To observe the distribution law of each phase in the material and the change of composite surface structure after the friction and wear experiment, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the micro-structure, friction film, debris, and friction cross section of the composites. The results show that the large particle size of copper-coated graphite is anisotropic in the material, which helps to form a friction film with a high graphite content on the contact surface. TEM images of the friction film and debris directly reflect the structure changes of graphite and copper during friction; under normal load and shear force, interlamellar detachment and interlamellar fracture of graphite occur, and its edge is folded and crimped, resulting in the loss of an ordered state in some regions, which results in the instability of crystal lattice and the transition from an ordered to disordered state of graphite, resulting in the (002) halo ring in FFT results. Severe plastic deformation and oxidation reactions occur in copper, and copper oxides are formed, forming a high-strength and smooth oxide film in the metal-rich area and improving the wear resistance of the material. TEM images of the friction section directly show that an inverted triangular deformation zone is formed on the surface of the sample after friction and wear experiments. The edge of the deformation zone is stepped, consisting of a drag zone and an accumulation zone, and the surface of the contact zone is covered by a carbon film.