Search

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12–1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10–1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

Background People living with HIV (PLWH) have a worse prognosis than the general population. Locally advanced or metastatic bladder cancer (BCa) in PLWH has gradually been increasing in recent years. Immune checkpoint inhibitors can improve antitumor activity in the general population, but relevant data in PLWH are unknown. We thus evaluated the efficacy and safety of tislelizumab in PLWH with locally advanced or metastatic BCa. Methods This retrospective study included 24 patients with locally advanced or metastatic BCa, both HIV positive or negative who underwent tislelizumab treatment (200 mg i.v. every 3 weeks, Q3W) from the multi-centers between December 2019 and March 2022. Demographic details, clinical data, and cancer status were collected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and treatment-related adverse events (TRAEs) were recorded and evaluated. Results A total of 24 individuals were chosen for this study, 10 had HIV and the other 14 did not. The median OS in the HIV-negative group was 62.3 (95% CI, 52.6 to 72.2) was no longer than that of the PLWH group 41.9 (95% CI, 32.9 to 51.0) weeks (HR .7, [95% CI, .17 to 3.30], P = .70). Furthermore, the median PFS in the HIV-negative group was 50.0 (95% CI, 36.2 to 63.9) was also no longer than that of the PLWH group 35.9 (95% CI, 25.5 to 46.3) (HR, 1.34, [95% CI, .38 to 4.69], P = .63). Of 24 patients, treatment-related adverse events, grade 3 or 4 occurred in 2 in the PLWH group and 3 in the HIV-negative group. Conclusion This retrospective multi-center study suggested that tislelizumab may provide encouraging antitumor activity and could be generally well tolerated. In this retrospective analysis of patients with locally advanced or metastatic BCa, it seems that PLWH may have similar overall and progression-free survival compared to HIV-negative cases.

The effect of graphite powder on the machining characteristics in graphite-powder-mixed electrochemical discharge machining of microholes was still not clear. How the discharge mechanism changed with the addition of graphite powder into the electrolyte, which further led to changes in the morphology of the machined holes, remained to be revealed. In this study, a series of microhole machining experiments were conducted in glass. Comparisons of the discharge energy, microhole entrance diameter, hole taper, and tool electrode morphology after machining were made when machining in the electrolytes with and without graphite powder. Experimental results revealed that there were a lot of small pulse currents distributed on the current waveform when machining with the graphite-powder-mixed electrolyte. The average discharge energy of the small pulse current was 2.8 times as much as that of the general electrochemical discharge. After introducing graphite powder into the electrolyte, the entrance diameter of the hole became larger when the hole depth was deeper than 200 μm. The HAZ width increased with increasing hole depth at the voltage of 37–41 V, while it decreased at the voltage of 43 V. A reduction in hole taper angle with a range of 0.5° to 2.3° was achieved. In addition, after machining in electrolytes with and without graphite powder, the tool electrode surfaces showed different morphologies due to different discharges.

The use of flexible, built-in, ultra-high-frequency (UHF) antenna sensors is an effective method to solve the weak high-frequency electromagnetic wave signal sensing of partial discharge (PD) inside gas-insulated switchgears (GISs), and the compatibility of flexible UHF antenna sensor substrate materials and SF6/N2 mixtures is the key to the realization of a flexible UHF antenna sensor inside a GIS. Based on this, this paper builds an experimental platform for the compatibility of a 30% SF6/70% N2 gas mixture and a PD flexible UHF antenna sensor substrate and conducts compatibility experiments between the 30% SF6/70% N2 gas mixture and PD flexible UHF antenna sensor substrate under different temperatures in combination with the actual operating temperature range of the GIS. In this article, a Fourier transform infrared spectrometer, scanning electron microscope and X-ray photoelectron spectrometer were used to test and analyze the gas composition, the surface morphology and the elemental change in the PD flexible UHF antenna sensor substrate, respectively. PET material will be slightly oxidized under the environment of a 30% SF6/70% N2 gas mixture at 110 °C, PI material will generate metal fluoride under the environment of a 30% SF6/70% N2 gas mixture and only PDMS material will remain stable under the environment of a 30% SF6/70% N2 gas mixture; therefore, it is appropriate to use PDMS substrate in the development of flexible UHF antenna sensors.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.

Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients’ quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.

This study explored the global cyberspace security issues, with the purpose of breaking the stereotype of people’s cognition of cyberspace problems, which reflects the relationship between interdependence and association. Based on the Apriori algorithm in association rules, a total of 181 strong rules were mined from 40 target websites and 56,096 web pages were associated with global cyberspace security. Moreover, this study analyzed support, confidence, promotion, leverage, and reliability to achieve comprehensive coverage of data. A total of 15,661 sites mentioned cyberspace security-related words from the total sample of 22,493 professional websites, accounting for 69.6%, while only 735 sites mentioned cyberspace security-related words from the total sample of 33,603 non-professional sites, accounting for 2%. Due to restrictions of language, the number of samples of target professional websites and non-target websites is limited. Meanwhile, the number of selections of strong rules is not satisfactory. Nowadays, the cores of global cyberspace security issues include internet sovereignty, cyberspace security, cyber attack, cyber crime, data leakage, and data protection.

Post-translational modifications (PTMs) are crucial mechanisms that underlie the intricacies of biological systems and disease mechanisms. This review focuses on the latest advancements in the design of heterobifunctional small molecules that hijack PTM machineries for target-specific modifications in living systems. A key innovation in this field is the development of proteolysis-targeting chimeras (PROTACs), which promote the ubiquitination of target proteins for proteasomal degradation. The past decade has seen several adaptations of the PROTAC concept to facilitate targeted (de)phosphorylation and acetylation. Protein fusion tags have been particularly vital in these proof-of-concept studies, aiding in the investigation of the functional roles of post-translationally modified proteins linked to diseases. This overview delves into protein-tagging strategies that enable the targeted modulation of ubiquitination, phosphorylation, and acetylation, emphasizing the synergies and challenges of integrating heterobifunctional molecules with protein tags in PTM research. Despite significant progress, many PTMs remain to be explored, and protein tag-assisted PTM-inducing chimeras will continue to play an important role in understanding the fundamental roles of protein PTMs and in exploring the therapeutic potential of manipulating protein modifications, particularly for targets not yet addressed by existing drugs.

The rotary energy recovery device (RERD) is integral in reducing energy consumption in desalination processes. The absence of a physical piston in RERD ducts allows salinity transfer from the brine to the seawater stream, which reduces RERD efficiency. To address this challenge, this study investigates the potential of utilizing splitter plates as a flow control technique to decrease the mixing degree within RERDs. Numerical simulations were performed to examine five different splitter plate configurations in RERD ducts in order to identify optimal designs for reducing the mixing degree. The analysis of internal streamlines and vortex distributions revealed that horizontal splitter plates positioned at the duct inlet effectively suppressed swirling flows, while splitter plates positioned at the center of the duct suppressed the formation of flow-induced vortices. This resulted in a more uniform salinity distribution and a reduction in the mass transfer rate between brine and seawater streams. The most significant reduction in the volumetric mixing rate was observed when employing cross-spread splitter plates positioned at the center of the duct. This paper presents an innovative method to reduce the mixing degree in the RERD.

The rotary energy recovery device (RERD) is an essential component in seawater desalination for decreasing the energy consumption of reverse osmosis plants. To research the complex flow fields and mixing motion in ducts of a rotary energy recovery device, a 3D numerical simulation was studied in this work. Three-dimensional vortex structures were visualized and identified based on the Q criterion. The effects of the operating condition and the structure parameter on the flow fields and the mixing motion had been discussed. Simulation results indicated that the interaction between vortices in the mixing zone and vortices in the duct entrance led to a high level of turbulence intensity and mixing degree. The mixing process could be controlled by the operating condition and the structure parameter. This paper provides a new approach to researching structural and operating factors on the mixing process of the rotary energy recovery device.

Studying electrophile signaling is marred by difficulties in parsing changes in pathway flux attributable to on-target, vis-à-vis off-target, modifications. By combining bolus dosing, knockdown, and Z-REX—a tool investigating on-target/on-pathway electrophile signaling, we document that electrophile labeling of one zebrafish-Keap1-paralog (zKeap1b) stimulates Nrf2- driven antioxidant response (AR) signaling (like the human-ortholog). Conversely, zKeap1a is a dominant-negative regulator of electrophile-promoted Nrf2-signaling, and itself is nonpermissive for electrophile-induced Nrf2-upregulation. This behavior is recapitulated in human cells: (1) zKeap1b-expressing cells are permissive for augmented AR-signaling through reduced zKeap1b–Nrf2 binding following whole-cell electrophile treatment; (2) zKeap1a-expressing cells are non-permissive for AR-upregulation, as zKeap1a–Nrf2 binding capacity remains unaltered upon whole-cell electrophile exposure; (3) 1:1 ZKeap1a:zKeap1b-co-expressing cells show no Nrf2-release from the Keap1-complex following whole-cell electrophile administration, rendering these cells unable to upregulate AR. We identified a zKeap1a-specific point-mutation (C273I) responsible for zKeap1a’s behavior during electrophilic stress. Human-Keap1(C273I), of known diminished Nrf2-regulatory capacity, dominantly muted electrophile-induced Nrf2-signaling. These studies highlight divergent and interdependent electrophile signaling behaviors, despite conserved electrophile sensing.

Acute ischemic stroke is a consequence of disrupted blood flow to the brain, caused by thrombosis—the pathological formation of occlusive clots within blood vessels, which can embolize distally to downstream tissues and microvasculature. The highest priority of stroke treatment is the rapid removal of occlusive clots and restoration of tissue perfusion. Intravenous thrombolysis is the pharmacological standard-of-care for the dissolution of blood clots, wherein thrombolytic drugs are administered to restore vessel patency. While the introduction of recombinant tissue-plasminogen activator (rtPA) in 1996 demonstrated the benefit of acute thrombolysis for clot removal, this was countered by severe limitations in terms of patient eligibility, lytic efficacy, rethrombosis and safety implications. Development of safer and efficacious treatment strategies to improve clot lysis has not significantly progressed over many decades, due to the challenge of maintaining the necessary efficacy-safety balance for these therapies. As such, rtPA has remained the sole approved acute therapeutic for ischemic stroke for over 25 years. Attempts to improve thrombolysis with coadministration of adjunct antithrombotics has demonstrated benefit in coronary vessels, but remain contraindicated for stroke, given all currently approved antithrombotics adversely impact hemostasis, causing bleeding. This Perspective provides a brief history of stroke drug development, as well as an overview of several groups of emerging drugs which have the potential to improve thrombolytic strategies in the future. These include inhibitors of the platelet receptor glycoprotein VI and the signaling enzyme PI3-Kinase, novel anticoagulants derived from hematophagous creatures, and proteolysis-targeting chimeras.

The chloroplast genomic information was obtained from three wild Solanum and four hybrids by chloroplast genome sequencing. The chloroplast genomes of the seven samples comprise of a circular structure and sizes from 155,581 to 155,612 bp and composed of 130 genes. The genome structures of the two hybrids were identical, while the other two hybrids showed 2 bp differences in the LSC when compared with their maternal parent. The total sites of SNP and InDel were 39–344 and 54–90, respectively. With the exception of one hybrid with two additional sites, the other hybrids were identical to their maternal.

Cells employ post-translational modifications (PTMs) as key mechanisms to expand proteome diversity beyond the inherent limitations of a concise genome. The ability to incorporate post-translationally modified amino acids into protein targets via chemical ligation of peptide fragments has enabled the access to homogeneous proteins bearing discrete PTM patterns and empowered functional elucidation of individual modification sites. Native chemical ligation (NCL) represents a powerful and robust means for convergent assembly of two homogeneous, unprotected peptides bearing an N-terminal cysteine residue and a C-terminal thioester, respectively. The subsequent discovery that protein cysteine residues can be chemoselectively desulfurized to alanine has ignited tremendous interest in preparing unnatural thiol-derived variants of proteogenic amino acids for chemical protein synthesis following the ligation-desulfurization logic. Recently, the 21st amino acid selenocysteine, together with other selenyl derivatives of amino acids, have been shown to facilitate ultrafast ligation with peptidyl selenoesters, while the advancement in deselenization chemistry has provided reliable bio-orthogonality to PTMs and other amino acids. The combination of these ligation techniques and desulfurization/deselenization chemistries has led to streamlined synthesis of multiple structurally-complex, post-translationally modified proteins. In this review, we aim to summarize the latest chemical synthesis of thiolated and selenylated amino-acid building blocks and exemplify their important roles in conquering challenging protein targets with distinct PTM patterns.

Eggplant is an important vegetable crop because of its rich nutrition, but to date no mitochondrial genome has been reported. In this study, the complete mitochondrial genome of the eggplant was sequenced. The complete mitochondrial genome was 498,136bp, linear structure, containing 54 protein-coding genes, four rRNAs, and 32 tRNAs. The phylogenetic tree supported the hypothesis that the eggplant is most closely related to Solanum tuberosum and Solanum lycopersicum.

Wild relatives represent a source of variation for many traits of interest for eggplant (Solanum melongena) breeding, as well as for broadening its genetic base. However, interspecific hybridization with wild relatives has been barely used in eggplant breeding programs, and reproductive barriers have resulted in reduced seed numbers in interspecific combinations. The mechanism underlying this phenomenon remains unclear. We hybridized females of cultivated eggplant 177 (Solanum melongena) with males of wild relatives 53 and Y11 (Solanum aethiopicum). Self-crossed 177 was the control. The seed number per control fruit was significantly higher than that of the hybrids. Paraffin sections showed no significant difference between control and 177×53 and 177×Y11. Double fertilization began 4 days post-pollination. Sperm cells were fused with egg cells 6 days post-pollination. To understand the differences in molecular mechanisms underlying this process, transcriptomes of ovaries at 0, 4, and 6 days after self-crossing and hybridization were analyzed. We screened 22,311 differentially expressed genes (DEGs) between the control and hybrids 4 and 6 days post-pollination. A total of 497 DEGs were shared among all pollination combinations. These DEGs were enriched in plant hormone transduction, cell senescence, metabolism, and biosynthesis pathways. DEG clustering analysis indicated distinct expression patterns between the control and hybrids but not between the hybrids. The DEGs in hybrids involved secondary metabolic process, phenylpropanoid metabolic process, and carboxypeptidase activity, while those in the control involved xyloglucan metabolic process, auxin-activated signaling pathway, cell wall polysaccharide metabolic process, and xyloglucosyl transferase activity. Additionally, 1683 transcription factors, including members of the AP2-ERF, MYB, bHLH, and B3 families may play important roles in self-crossing and hybridization. Our results provide insights into the regulatory mechanisms underlying variations between ovaries of self-crossed and hybrid eggplants and a basis for future studies on crossbreeding Solanum and genetic mechanisms underlying double fertilization.

As an important part of the quadruped robot, the leg determines its performance. Flexible legs or flexible joints aid in the buffering and adaptability of robots. At present, most flexible quadruped robots only have two-dimensional flexibility or use complex parallel structures to achieve three-dimensional flexibility. This research will propose a new type of three-dimensional flexible structure. This passive compliant three-dimensional flexibility reduces the weight and complex structure of the robot. The anti-impact performance of the robot is verified by a side impact experiment. The simulation and experiments show that the robot still has good stability even under a simple algorithm and that the flexible leg can reduce the impact on the quadruped robot and improve the environmental adaptability of the robot.

Here we discuss, how by applying chemical concepts to biological problems, methods have been developed to map spatiotemporal regulation of proteins and small-molecule modulation of proteome signaling responses. We outline why chemical-biology platforms are ideal for such purposes. We further discuss strengths and weaknesses of chemical-biology protocols, contrasting them against classical genetic and biochemical approaches. We make these evaluations based on three parameters: occupancy; functional information; and spatial restriction. We demonstrate how the specific choice of chemical reagent and experimental set-up unite to resolve biological problems. Potential improvements/extensions as well as specific controls that in our opinion are often overlooked or employed incorrectly are also considered. Finally, we discuss some of the latest emerging methods to illuminate how chemical-biology innovations provide a gateway toward information hitherto inaccessible by conventional genetic/biochemical means. Finally, we also caution against solely relying on chemical-biology strategies and urge the field to undertake orthogonal validations to ensure robustness of results.