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Abstract Background Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. Methods This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. Results GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors—including smoking, alcohol consumption, major depression, and body mass index (BMI)—these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14–1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03–1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19–1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22–2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23–5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. Conclusions This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies.

A new newt species, Hypselotriton huanggangensis sp. nov., is described based on nine specimens collected from Huanggangshan Mountains, Yanshan County, Jiangxi, China. Morphologically, the new species is characterized by the combination of nine external characters: (1) obvious black patches with clear boundaries on the whole body; (2) ground color of the dorsal body tan; (3) ground color of venter bright orange; (4) skin rough; (5) vertebral ridge weak; (6) fingers and toes overlapping when forelimb and hindlimb adpressed towards each other along body; (7) postocular orange spot absent; (8) small white warty glands around the eye; (9) two discontinuous longitudinal lines formed by white warty glands from neck to lateral parts of tail. Molecularly, the new species forms an independent clade with strong support in the phylogenetic trees of the genus based on the mitochondrial locus of NADH dehydrogenase subunit 2 (ND2) gene fragments. The new species distinctly differs from H. fudingensis by differences in its body measurements, vertebral ridge, dorsal black patches, and ventral black patches. Furthermore, the new species and H. fudingensis are geographically isolated by a series of high mountain ranges, including the Wuyishan and Jiufengshan Mountains. The number of Hypselotriton species is now 11.

Abstract Background Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear. Methods Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings. Results A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer. Conclusion This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies.

Abstract Artificial wrinkles, especially those with responsive erasure/regeneration behaviors have gained extensive interest due to their potential in smart applications. However, current wrinkle modulation methods primarily rely on network rearrangement, causing bottlenecks in in situ wrinkle regeneration. Herein, we report a dually cross-linked network wherein [2]rotaxane cross-link can dissipate stress within the wrinkles through its sliding motion without disrupting the network, and quadruple H-bonding cross-link comparatively highlight the advantages of [2]rotaxane modulation. Acid stimulation dissociates quadruple H-bonding and destructs network, swiftly eliminating the wrinkles. However, the regeneration process necessitates network rearrangement, making in situ recovery unfeasible. By contrast, alkaline stimulation disrupts host–guest recognition, and subsequent intramolecular motion of [2]rotaxane dissipate energy to eliminate wrinkles gradually. The always intact network allows for the in situ recovery of surface microstructures. The responsive behaviors of quadruple H-bonding and mechanical bond are orthogonal, and their combination leads to wrinkles with multiple but accurate responsiveness.

Abstract Background Prostate cancer, characterized by its insidious onset and short overall survival, and has seen a rise in incidence over recent decades. This study aims to investigate the expression and molecular mechanism of lncRNA PTCSC3 (PTCSC3) in prostate cancer in order to develop new prognostic and therapeutic biomarkers. Methods The level of PTCSC3 in serum and cell samples of prostate cancer was quantitatively measured using RT-qPCR assays. The correlation between the variation in PTCSC3 levels and clinical indicators of patients was evaluated. The survival status of the prostate cancer patients included in the study was evaluated using Kaplan-Meier curve and multivariable Cox analysis. The impact of PTCSC3 overexpression on cell growth and activity was revealed by CCK-8 and Transwell assays. The targeting relationship between PTCSC3 and miR-182-5p was determined by bioinformatics prediction and luciferase activity. Results PTCSC3 was found to be downregulated in prostate cancer, and its low levels were associated with short overall survival in patients. It influenced the progression of prostate cancer by targeting miR-182-5p. Increasing PTCSC3 levels suppressed the proliferation, migration and invasion levels of cells, and miR-182-5p mimic counteracted PTCSC3’s effects on cells. Conclusions As a potential prognostic biological factor for prostate cancer, PTCSC3 may regulate the progression of prostate cancer by sponging miR-182-5p and affect the prognosis of patients.

Objective Thoracolumbar fractures are one of the most common fractures in clinical practice. Surgical intervention is recommended to restore spinal alignment or decompress the nerves when there are unstable fractures or neurological injuries. However, after excessive forward thrust force restoration, facet joint dislocation often occurs between the upper vertebra and the fractured vertebra, which usually leads to unsatisfactory reduction outcomes. Herein, we propose a novel spinal facet joint toothed plate to assist in fracture reduction. The purpose of this study is to evaluate the effectiveness of the new spinal facet joint toothed plate in preventing facet joint dislocation, and its advantages compared to traditional pedicle screw‐rod decompression. Methods A total of 26 patients in the toothed plate group and 93 patients in the traditional group who experienced thoracolumbar fracture with reduction were retrospectively included. Relevant patients' information and clinical parameters were collected. Furthermore, visual analogue scores (VAS) scores and Oswestry disability index (ODI) scores were also collected. Moreover, imaging parameters were calculated based on radiographs. Correlated data were analyzed by χ2 test and t test. Results All patients in this study had no postoperative complications. Postoperative VAS scores and ODI scores (p

Abstract When some new‐type sensors are subjected electromagnetic interference (EMI), the traditional standard can no longer serve as the guidance for their EMI protection. Therefore, it is necessary to evaluate the complexity of the new sensing equipment's suffering from electromagnetic interference. A hybrid method of feature extraction and complexity evaluation of Electromagnetic Interference signals based on generalised correntropy criterion (GCC) is proposed. First, a variational mode decomposition algorithm for adaptive extraction of decomposed signals is constructed using GCC, and Generalised S‐transform is used for processing and reorganisation. Then, according to the time‐frequency space model, a new quantitative evaluation criterion interference factor is proposed, which overcomes the shortcomings of the traditional qualitative classification and the inability to solve the cross classification of indicators. Then, the Gated Recurrent Unit is introduced, and the GCC‐GRU evaluation model with GCC as the loss function is derived. The authors conduct EMI tests and measured signal evaluation with Medium Voltage and High Voltage switches, and the results show that the method proposed is correct and effective.

Abstract Background Migraine, a neurological disorder with a significant female predilection, is the leading cause of disability-adjusted life years (DALYs) in women of childbearing age (WCBA). There is currently a lack of comprehensive literature analysis on the overall global burden and changing trends of migraines in WCBA. Methods This study extracted three main indicators, including prevalence, incidence, and DALYs, related to migraine in WCBA from the Global Burden of Disease(GBD) database from 1990 to 2021. Our study presented point estimates with 95% uncertainty intervals (UIs). It evaluated the changing trends in the burden of migraine in WCBA using the estimated annual percentage change (EAPC) and percentage change. Results In 2021, the global prevalence, incidence, and DALYs cases of migraine among WCBA were 493.94 million, 33.33 million, and 18.25 million, respectively, with percentage changes of 48%, 43%, and 47% compared to 1990. Over the past 32 years, global prevalence rates and DALYs rates globally have increased, with an EAPC of 0.03 (95% UI: 0.02 to 0.05) and 0.04 (95% UI: 0.03 to 0.05), while incidence rates have decreased with an EAPC of -0.07 (95% UI: -0.08 to -0.05). Among the 5 Socio-Demographic Index (SDI) regions, in 2021, the middle SDI region recorded the highest cases of prevalence, incidence, and DALYs of migraine among WCBA, estimated at 157.1 million, 10.56 million, and 5.81 million, respectively, approximately one-third of the global total. In terms of age, in 2021, the global incidence cases for the age group 15–19 years were 5942.5 thousand, with an incidence rate per 100,000 population of 1957.02, the highest among all age groups. The total number of migraine cases and incidence rate among WCBA show an increasing trend with age, particularly in the 45–49 age group. Conclusions Overall, the burden of migraine among WCBA has significantly increased globally over the past 32 years, particularly within the middle SDI and the 45–49 age group. Research findings emphasize the importance of customized interventions aimed at addressing the issue of migraines in WCBA, thus contributing to the attainment of Sustainable Development Goal 3 set by the World Health Organization.

Considering the negative effects of wetland degradation, various measures have been implemented to restore wetland habitats for aquatic organisms, and their effectiveness levels must be assessed. To reduce the effects of aquaculture on aquatic communities, pen culture facilities, which are widely distributed in Yangtze-connected lakes, were removed in 2018. We surveyed and compared waterbird communities in Caizi Lake during the four months before (2017–2018) and after net pen removal (2021–2022) to evaluate their effect on the diversity and species composition of wintering waterbirds. After net pen removal, the richness and number of individual waterbird species increased, whereas the Shannon–Wiener diversity index did not change because the increase in the bird number throughout the year was mostly associated with a few species. The response of individual numbers of different guilds to the removal of net pens differed. The number of deep-water fish eaters, seed eaters, and tuber feeders increased, whereas that of invertebrate eaters decreased. The species composition also changed, particularly in the northeastern and southwestern parts of the lake. Differences in waterbird communities between the winters of 2017–2018 and 2021–2022 indicated that net pen removal had a positive impact on waterbird communities.

The effects of deoxidation methods on the inclusion characteristics and corrosion behaviour of high-strength low-alloy steels were examined in marine environments using various microcharacterisation techniques and first-principles calculations. After Ca treatment, MnS–MgO–Al2O3 inclusions were modified to CaS–MgO–Al2O3 and microcrevices were existed at the interface between inclusions and Fe. After Zr–Ti-RE deoxidation, spherical CaS + TiN + ZrO2+MgAl2O4+(Ca, La) Al3O7 inclusions appeared. (Ca, La)Al3O7 in steel displayed similar mechanical properties to Fe, reducing the degree of lattice distortion and the formation of microcrevices around the inclusions. Micro-galvanic corrosion between Fe and MnS accelerated the localised corrosion rate and promoted the formation of large pits on the surface. However, the chemical activity of CaS resulted in dissolution of the inclusion, which relatively inhibited the localised corrosion propagation. The enrichment of Cr in the rust layer after Zr–Ti-RE deoxidation improved the compactness, contributed to a reduction in the localised corrosion rate and long-term corrosion rate. Finally, the underlying mechanism influencing corrosion behaviour was established.

Objective To study and compare the effects of different storage temperature and time on coagulation factor after cryoprecipitated antihemophilic factor(CAF) melting, and to provide reference for the establishment of industry standards. Methods From June 2021 to May 2023, a total of 96 bags of CAF were sampled in 4 bags per month, and timely detected in the same month. After the CAF was melted in a 37℃ water bath, the mild to moderate lipemic blood was labeled. Each bag of CAF and two 50 mL transfer bags were divided into two bags and two groups of 20 mL each using a sterile adapter. One group was placed in a 4℃ refrigerator and the other in a 22℃ water bath for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h. Then 2 mL of aseptic sample was taken separately and put into the test tube, and 1mL of sample and 3 mL of buffer were added into the other test tube with the sampling gun and mixed on the machine for testing. The experimental data of 60 bags without mild to moderate lipemic blood cryoprecipitation and coagulation factor were randomly selected and statistically analyzed by SPSS21.0. Results After melting, CAF was stored for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h to detect the average content and growth rate of coagulation factor in the two groups: 1) Storage at 4℃, factor Ⅷ content was 118.62, 111.57(-5.95%), 105.51(-11.05%), 103.30(-12.92%), 94.35(-20.46%) and 83.25(-29.82%) IU/ bag, respectively; Storage at 22℃, the factor Ⅷ content was 118.62, 112.69(-5.00%), 111.41(-6.08%), 109.01(-8.10%), 101.55(-14.39%) and 92.75(-21.81%) IU/ bag, and the storage results of the two groups were compared. At 24 h at 4℃ and 48 h at 22℃, the content of factor Ⅷ had significant statistical significance(P0.05). Conclusion After CAF melting, coagulation factor decreased with the extension of storage time, especially the decrease of factor Ⅷ, followed by factor V, while Fbg basically unchanged. Comparison between the two groups showed that, factor Ⅷ decay rate is slower, factor V decay rate is faster of storage at 22℃. CAF should be transfused as soon as possible after melting. If the delay is unavoidable, for the delay time less than 12 h, storage at 4℃ is recommended, fot the delay time more than 12 h and less than 24 h, storage at 22℃ is recommended.

Abstract Purpose The purpose of this study was to investigate the role of lncRNA DSCAM-AS1 in prostate cancer to find new therapeutic targets and promote the research progress of prostate cancer. Methods RT-qPCR was used to detect DSCAM-AS1 expression in prostate cancer tissues, normal tissues, human normal prostate epithelial cells (RWPE), and four prostate cancer cell lines. The clinical and prognostic role of DSCAM-AS1 was evaluated by the Kaplan–Meier curve and chi-square test. Secondly, a dual luciferase reporter gene assay was used to study the regulatory mechanism between miR-338-3p and DSCAM-AS1. Finally, the roles of DSCAM-AS1 and miR-338-3p in prostate cancer cell proliferation and metastasis were explored by CCK-8 and Transwell assays. Results It was found that DSCAM-AS1 upregulation could serve as a warning of deterioration and poor prognosis in prostate cancer patients, and that knockdown of DSCAM-AS1 expression inhibited the progression of prostate cancer cells. In addition, miR-338-3p, a target of DSCAM-AS1, was found to be down-regulated in prostate cancer cells and miR-338-3p knockdown could reverse the inhibitory effect of DSCAM-AS1 silencing on prostate cancer. Conclusion DSCAM-AS1 is up-regulated in prostate cancer and regulates the progression of prostate cancer cells by targeting miR-338-3p.

PurposeTo explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved.MethodsNew Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA).ResultsDifferent molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following.ConclusionsIn the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.

Abstract Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α‐helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS‐CoV‐2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross‐neutralize the bat‐ and pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, and PCoV‐GX) and other human CoVs (SARS‐CoV, MERS‐CoV, HCoV‐NL63, and HCoV‐229E). Fourth, IPB29 administrated as an inhalation solution (IPB29‐IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS‐CoV‐2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29‐IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS‐CoV‐2 and other coronaviruses.

Flight safety in helicopters is a critical aspect of overall aircraft operational safety management, particularly during engine failures requiring autorotative glide, which makes it extremely challenging for the pilot to land the helicopter successfully. In this study, we evaluated the workload and attention allocation of helicopter pilots under such circumstances. In the experiment, a helicopter flight simulator was used to simulate level flight followed by autorotative glide, with the two phases divided into time segments for data collection. First, the data were visualized using heat maps and saccade sequence diagrams, while changes in eye movement metrics (such as peak value and standard deviation) were statistically analyzed. Finally, the criteria through the inter-criteria correlation (CRITIC) method was used to calculate the weight coefficient for each area of interest. This evaluation system was further applied to analyze and compare the changes in eye-movement data and attention to areas of interest during the two phases. The results revealed a shorter fixation duration, but a greater fixation number during the autorotative glide phase. Further, the mean pupil diameter changed over a larger range than during level flight (in level flight, the mean was 5.229 mm, while the standard deviation was 0.059 mm; in autorotative glide the corresponding values were 5.326 mm and 0.126 mm, respectively). For the tachometer, the weight coefficient matched the color of the heat map (2.7 % and colorless during level flight, but 23.8 % and red during autorotative glide), while those for the airspeed indicator and forward view differed significantly between the two phases. This discrepancy stemmed from the fact that during autorotative glide, the pilots prioritized monitoring aircraft rotation speed and attitude, with a particular focus on the forward view, rotor speed, and airspeed, resulting in a more concentrated attention distribution compared to that achieved during level flight. These results confirmed a significant increase in pilot workload during autorotative glide landing, while a shift was observed from low-frequency long gaze time during level flight to high-frequency short gaze time during autorotative glide. Furthermore, the pilots allocated 81 % of their attention to the tachometer, airspeed indicator, and forward views. Adopting this strategy can improve pilots’ landing success and provide flight students with valuable training advice to prevent landing failures when helicopters lose power.

Background: Aged sarcopenia is characterized by loss of skeletal muscle mass and strength, and mitochondrial dysregulation in skeletal myocyte is considered as a major factor. Here, we aimed to analyze the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on mitochondrial reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in aged skeletal muscles. Methods: C2C12 cells were stimulated by 50 μM 7β-hydroxycholesterol (7β-OHC) to observe the changes of cellular ROS, mitochondrial ROS, and expression of PGC-1α and Nrf2. Different PGC-1α expression in cells was established by transfection with small interfering RNA (siRNA) or plasmids overexpressing PGC-1α (pEX-3-PGC-1α). The effects of different PGC-1α expression on cellular ROS, mitochondrial ROS and Nrf2 expression were measured in cells. Wild type (WT) mice and PGC-1α conditional knockout (CKO) mice were used to analyze the effects of PGC-1α on aged sarcopenia and expression of Nrf2 and CD38 in gastrocnemius muscles. Diethylmaleate, a Nrf2 activator, was used to analyze the connection between PGC-1α and Nrf2 in cells and in mice. Results: In C2C12 cells, the expressions of PGC-1α and Nrf2 were declined by the 7β-OHC treatment or PGC-1α silence. Moreover, PGC-1α silence increased the harmful ROS and decreased the Nrf2 protein expression in the 7β-OHC-treated cells. PGC-1α overexpression decreased the harmful ROS and increased the Nrf2 protein expression in the 7β-OHC-treated cells. Diethylmaleate treatment decreased the harmful ROS in the 7β-OHC-treated or PGC-1α siRNA-transfected cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia, decreased Nrf2 expression and increased CD38 expression in gastrocnemius muscles compared with the WT mice. Diethylmaleate treatment improved the muscle function and decreased the CD38 expression in the old two genotypes. Conclusions: Our study demonstrated that PGC-1α modulated mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2.

Abstract Neuropeptide Y (NPY), a 36‐amino‐acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]–NPY and [Leu31, Pro34]–NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N‐terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor‐selective drug development. In this study, we report three cryo‐electron microscopy (cryo‐EM) structures of Gi2‐coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]–NPY. Combined with cell‐based assays, our study not only reveals the conserved peptide‐binding mode of NPY receptors but also identifies an additional sub‐pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub‐pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.

This paper presents the dynamic voltage stability index based on the voltage oscillation loop for power systems integrated with multiple permanent magnet synchronous generators (PMSGs) to assess the dynamic interaction on voltage stability. First, the model of power systems integrated with multi-PMSGs using a Q–V sensitivity matrix as feedback to connect all PMSGs is established. The transfer function model between voltage and reactive power is derived, and the voltage oscillation loop can be derived, which exists in each PMSG. Next, the dynamic voltage stability index is theoretically derived and given, the impact of dynamic interaction among multi-PMSGs on voltage stability can be quantified, and the source of voltage oscillation can be identified and determined. Then, the voltage stability is recovered by shedding the trouble-making PMSG. The parameters of PMSGs could be tuned with the guidance of the dynamic voltage stability index to reduce the risk of voltage oscillation. Finally, the example of a test system with PMSGs is used to validate the correctness of the dynamic stability index.

The United Nations’ Sustainable Development Goals (SDGs) are significant in guiding modern scientific research. In recent years, scholars have paid much attention to MOFs materials as green materials. However, piezo catalysis of MOFs materials has not been widely studied. Piezoelectric materials can convert mechanical energy into electrical energy, while MOFs are effective photocatalysts for removing pollutants. Therefore, it is crucial to design MOFs with piezoelectric properties and photosensitivity. In this study, sulfur-functionalized metal–organic frameworks (S-MOFs) were prepared using organic sulfur-functionalized ligand (H2TDC) ultrasonic synthesis to enhance their piezoelectric properties and visible light absorption. The study demonstrated that the S-MOFs significantly enhanced the reduction of a 10 mg/L solution of hexavalent chromium to 99.4 % within 10 min, using only 15 mg of catalyst. The orbital energy level differences of the elements were analyzed using piezo response force microscopy (PFM) and X-ray photoelectron spectroscopy (XPS). The results showed that MOFs functionalized with sulfur atom ligands have a built-in electric field that facilitates charge separation and migration. This study presents a new approach to enhance the piezoelectric properties of MOFs, which broadens their potential applications in piezo catalysis and piezo-photocatalysis. Additionally, it provides a sustainable method for reducing hexavalent chromium, contributing to the achievement of sustainable development goals, specifically SDG-6, SDG-7, SDG-9, and SDG-12.

Objectives: To investigate the factors influencing imipenem/cilastatin (IMI) and meropenem (MEM) concentrations in critically ill adult patients and the role of these concentrations in the clinical outcome. Methods: Plasma trough concentrations of IMI and MEM were detected by high-performance liquid chromatography. A target value of 100%-time above MIC was used for the drugs. Results: A total of 186 patients were included, with 87 receiving IMI and 99 receiving MEM. The percentages of patients reaching the target IMI and MEM concentrations were 44.8% and 38.4%, respectively. The proportions of patients infected with drug-resistant bacteria were 57.5% and 69.7% in the IMI group and MEM group, respectively. In the multivariate analysis, the risk factors for an IMI concentration that did not reach the target were infection with drug-resistant bacteria, and those for MEM were infection with drug-resistant bacteria, estimated glomerular filtration rate, and diabetes mellitus. A total of 47.1% of patients had good outcomes in the IMI cohort, and 38.1% of patients had good outcomes in the MEM cohort. The duration of mechanical ventilation and IMI concentration were associated with ICU stay in patients in the IMI cohort, while MEM concentration and severe pneumonia affected the clinical outcome of patients in the MEM cohort. Conclusion: Infection with drug-resistant bacteria is an important factor influencing whether IMI and MEM concentrations reach the target. Furthermore, IMI and MEM concentrations are associated with the clinical outcome, and elevated doses of IMI and MEM should be given to patients who are infected with drug-resistant bacteria.

Based on the five main activation mechanisms, this study explored the potential activating elements in Al-based sacrificial anodes (SAs) combining electrochemical experiments and theoretical calculation. Mn, Y, Zr, Nb, and Ta, aligning with several activation mechanisms, are expected to be the potential activating elements besides the acknowledged activating elements (In, Sn, Ga, Zn, Bi). In addition, the negative shift of potential effect of In to Al matrix is denied both experimentally and theoretically. This study will contribute to establish a comprehensive understanding for the development of Al SAs.

Abstract Objective The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. Methods This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). Results Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein–protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. Conclusion Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

Abstract Background Theaceae, comprising 300 + species, holds significance in biodiversity, economics, and culture, notably including the globally consumed tea plant. Stewartia gemmata, a species of the earliest diverging tribe Stewartieae, is critical to offer insights into Theaceae's origin and evolutionary history. Result We sequenced the complete organelle genomes of Stewartia gemmata using short/long reads sequencing technologies. The chloroplast genome (158,406 bp) exhibited a quadripartite structure including the large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs); 114 genes encoded 80 proteins, 30 tRNAs, and four rRNAs. The mitochondrial genome (681,203 bp) exhibited alternative conformations alongside a monocyclic structure: 61 genes encoding 38 proteins, 20 tRNAs, three rRNAs, and RNA editing-impacting genes, including ATP6, RPL16, COX2, NAD4L, NAD5, NAD7, and RPS1. Comparative analyses revealed frequent recombination events and apparent rRNA gene gains and losses in the mitochondrial genome of Theaceae. In organelle genomes, the protein-coding genes exhibited a strong A/U bias at codon endings; ENC-GC3 analysis implies selection-driven codon bias. Transposable elements might facilitate interorganelle sequence transfer. Phylogenetic analysis confirmed Stewartieae's early divergence within Theaceae, shedding light on organelle genome characteristics and evolution in Theaceae. Conclusions We studied the detailed characterization of organelle genomes, including genome structure, composition, and repeated sequences, along with the identification of lateral gene transfer (LGT) events and complexities. The discovery of a large number of repetitive sequences and simple sequence repeats (SSRs) has led to new insights into molecular phylogenetic markers. Decoding the Stewartia gemmata organellar genome provides valuable genomic resources for further studies in tea plant phylogenomics and evolutionary biology.

The harsh environment of high alkalinity inhibits the effective induction of calcium carbonate precipitation by microorganisms within concrete. In this study, a gradient domestication method was employed to enhance the alkali tolerance of Sporosarcina pasteurii, and various activity parameters (OD600, conductivity, urease activity, and calcium carbonate content) were assessed in an alkaline cultivation setting. Subsequently, a comprehensive evaluation was conducted to compare the impact of domesticated microorganisms on the mechanical properties, impermeability, and self-healing capacity of concrete. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were employed to characterize the morphology and composition of mineralization products. The results demonstrate that gradient domestication techniques effectively enhance the activity of microorganisms in highly alkaline environments and confirmed that enhanced alkalinity tolerance possesses the potential for multigenerational retention. In comparison to the undomesticated microbial samples at 28 d, concrete incorporating domesticated microorganisms exhibited a 16.59 % increase in compressive strength, a 37.74 % reduction in sorption, and a 23.08 % decrease in permeability. Additionally, the maximum closed crack width measured 0.57 mm, exceeding the 0.44 mm observed in the non-domesticated bacterial group. This study offers a promising strategy for improving the efficiency of microbial-induced calcium carbonate precipitation in concrete.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

When local discharge occurs inside the transformer, it will be accompanied by a burst sound to generate an ultrasonic signal, which can be used for fault monitoring and diagnosis inside the transformer. This paper focuses on studying the converter transformer and simulating and analyzing the location where local discharge is likely to occur in the converter transformer. The provided information includes the distribution of sound pressure within and outside the converter transformer and the impact of the winding on this distribution. Furthermore, the investigation focuses on the testing of local discharge in converter transformers using ultrasonic signals. A local discharge detection device for converter transformers has been developed. The experiment and analysis have been conducted, and what was learned was compared to the simulated outcomes. The determination of the local discharge position in converter transformers is based on the analysis of the time-varying waveform obtained at the observation point. This approach offers a novel method for finding and identifying local discharge.

To verify the predictive accuracy of existing strength criteria on true triaxial strength experimental data, understand the characteristics of different strength criteria, and provide a basis for selecting strength criteria for engineering applications, ten commonly used rock strength criteria were selected and divided into MC and HB types. The distribution characteristics of the yield surfaces and yield curves of different criteria were compared and analyzed in the principal stress space and the π plane. Afterwards, based on the least absolutely deviation method, these ten strength criteria were used to predict 32 sets of true triaxial rock strength experimental data. The results showed that the range of undetermined parameters for MC type strength criteria was small and easy to determine, while the range of undetermined parameter for HB type criteria was large and difficult to determine the search range, in addition, the fitting process may not converge. The fitting accuracy of strength criteria for true triaxial experimental data depends on the sensitivity of rock strength to the intermediate principal stress. PH and GP criteria are the most sensitive to changes of the intermediate principal stress, followed by MWC and ML criteria, MGC and ZZ criteria, MCJP and HBWW criteria. PH and GP criteria overestimate the effect of the intermediate principal stress, resulting in the largest prediction errors, while the other three-dimensional strength criteria have high prediction accuracy and no significant differences. The research results can provide scientific basis for engineering design, geological hazard prediction, and mineral resource development.

Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most cases of breast cancer. However, there is ongoing debate about any potential variations in overall survival (OS) between ILC and IDC. This study aimed to compare survival between IDC and ILC, identify prognostic factors for ILC patients, and construct a nomogram for predicting OS rates. This retrospective cohort analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Database. Patients diagnosed with ILC and IDC between 2000 and 2019 were enrolled. To minimize baseline differences in clinicopathological characteristics and survival outcomes, a propensity score matching (PSM) method was used. Data from the multivariate Cox regression analyses were used to construct a predictive nomogram for OS at 1, 3, and 5 years, incorporating all independent prognostic factors. Following the PSM procedure, patients with ILC exhibited a better prognosis compared to those with IDC. TNM stage, age >70, radiotherapy, surgery, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HR-/HER2+) subtype were identified as independent factors for OS in ILC patients. Surgery and radiotherapy effectively reduced the risk of death, while chemotherapy did not demonstrate the same benefit. This model could support clinicians in evaluating the prognosis of ILC for decision-making and patient counseling.

Background: Sarcomas rarely involve body cavity fluids, accounting for less than 5% of all malignant effusions. Most existing literature describes the cytomorphologic features of sarcomas in the setting of fine-needle aspiration and/or touch preparations of targeted tissue biopsies. The objective of this study was to investigate the morphologic spectrum displayed by metastatic sarcomas in body cavity fluid specimens. Methods: The pathology database at our institution was searched for sarcoma cases involving pleural, pericardial, and peritoneal fluids between 1994 and 2019. Their clinical presentations and cytopathologic features were reviewed. Immunohistochemical (IHC) stains were performed on the cellblock sections at our institution on the DAKO Autostainer (DAKO, Carpinteria, CA). Results: Nineteen cases were identified, including 14 females and 5 males, ranging in age from 4 to 88 years old (median: 28.6 years). The body cavity sites were 11 pleural, 7 peritoneal, and 1 pericardial. There were 5 rhabdomyosarcomas, 4 osteosarcomas, 4 Ewing sarcomas, 2 endometrial stromal sarcomas, 2 leiomyosarcomas, 1 clear cell sarcoma, and 1 liposarcoma. Malignant pleural effusion was the first presentation in only 2 cases (both alveolar rhabdomyosarcomas). Three different cytomorphologic patterns were seen: 1-glandular cell pattern showing large epithelioid cells with vacuolated cytoplasm (3 cases), a 2-pleomorphic single-cell pattern showing large highly atypical cells (6 cases); 3-small round blue cell pattern showing small to intermediate-sized dyscohesive cells with high NC ratio (10 cases). Conclusion: The cytomorphologic spectrum exhibited by metastatic sarcomas in body cavity fluids often overlaps with other common malignancies such as metastatic adenocarcinomas, poorly differentiated carcinomas, and lymphomas. Keywords: Sarcoma; Cytology; Peritoneal.

Cardiovascular disease (CVD) is a serious public health risk, and prevention and treatment efforts are urgently needed. Effective preventive and therapeutic programs for cardiovascular disease are still lacking, as the causes of CVD are varied and may be the result of a multifactorial combination. Mitophagy is a form of cell-selective autophagy, and there is increasing evidence that mitophagy is involved in cardioprotective processes. Recently, many studies have shown that FUN14 domain-containing protein 1 (FUNDC1) levels and phosphorylation status are highly associated with many diseases, including heart disease. Here, we review the structure and functions of FUNDC1 and the path-ways of its mediated mitophagy, and show that mitophagy can be effectively activated by dephosphorylation of Ser13 and Tyr18 sites, phosphorylation of Ser17 site and ubiquitination of Lys119 site in FUNDC1. By effectively activating or inhibiting excessive mitophagy, the quality of mitochondria can be effectively controlled. The main reason is that, on the one hand, improper clearance of mitochondria and accumulation of damaged mitochondria are avoided, and on the other hand, excessive mitophagy causing apoptosis is avoided, both serving to protect the heart. In addition, we explore the possible mechanisms by which FUNDC1-mediated mitophagy is involved in exercise preconditioning (EP) for cardioprotection. Finally, we also point out unresolved issues in FUNDC1 and its mediated mitophagy and give directions where further research may be needed.

ObjectiveLipid metabolism plays an important role in cancer. The aim of this study was to investigate the relationship between lipid metabolism and the development of cervical cancer, and to explore the prognostic significance of lipid metabolism-related genes in patients with cervical cancer.MethodsInitially, we retrospectively collected data from 1589 cervical cancer patients treated at the Affiliated Hospital of Qingdao University, with 1589 healthy individuals from the physical examination center serving as the control group. The correlation between their serum lipid levels and cervical cancer was analyzed. Subsequently, leveraging public databases, we conducted comprehensive studies on lipid metabolism-related genes. Additionally, we analyzed RNA expression profiling and clinical information sourced from TCGA and GTEx databases. Finally, we established a prognostic model integrating 9 genes associated with lipid metabolism and generated a nomogram model using R. GO and KEGG were performed to explore the functions and pathways of lipid metabolism-related genes.ResultsOur findings revealed that patients with cervical cancer exhibited dyslipidemia, characterized by elevated levels of TC, TG, and LDL-C, alongside reduced HDL-C levels compared to controls (P

Objective: Competitive endogenous RNA (ceRNA) networks have uncovered a novel mode of RNA interaction, and are implicated in various biological processes and the pathogenesis of IS. This study aimed to explore the potential mechanisms underlying the ceRNA network in IS. Methods: Four public datasets containing lncRNA and mRNA (GSE22255 and GSE16561) and miRNA (GSE55937 and GSE43618) expression profiles from the GEO database were systematically analyzed to explore the role of RNAs in ischemic stroke (IS). Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) between IS and normal control samples were identified. LncRNA-miRNA and miRNA-mRNA interactions were predicted, and the competing endogenous RNA (ceRNA) regulatory network was constructed using the Cytoscape software. The correlation between the RNAs in the ceRNA network and the clinical features of the samples was evaluated. Finally, principal component analysis was performed on the RNAs that constitute the ceRNA regulatory network, and their differential expression and principal component relationships among different types of samples were observed. Results: A total of 224 DEmRNAs, 7 DEmiRNAs, and four DElncRNAs related to IS in four datasets were identified. Then, through target gene prediction, a lncRNA–miRNA–mRNA ceRNA network that contained 3 DElncRNAs, 2 DEmiRNAs, and 24 DEmRNAs was constructed. Correlations of the clinical characteristics showed that PART1 and SERPINH1 were related to clinical diseases, WNK1 was related to lifestyle, and seven RNAs were related to age. PCA results indicate that three principal components of PC1, PC2, and PC3 can clearly distinguish between control and IS samples. Conclusion: Overall, we constructed a ceRNA network in IS, which could offer insights into the molecular mechanism and potential prognostic biomarkers for further research.

Background and aimsHyperthyroidism is an endocrine disease with multiple etiologies and manifestations. Heart failure (HF) is a common, costly, and deadly medical condition in clinical practice. Numerous studies have suggested that abnormal thyroid function can induce or aggravate the development of heart disease. However, no study has demonstrated a causal relationship between hyperthyroidism and heart failure. Therefore, the purpose of this study was to explore the causal link between hyperthyroidism and HF.MethodsSummary data for genetically predicted hyperthyroidism were obtained from a genetic association study. The data examined for genetically determined all-cause heart failure came from 218,208 individuals from the FinnGen Consortium. Two-sample Mendelian randomization (MR) analysis was used to estimate the causal link between hyperthyroidism and heart failure. Statistical analyses were conducted using the inverse variance-weighted, weighted median, simple median, weighted mode, MR-PRESSO (number of distribution = 5000), MR-Egger, and leave-one-out.ResultsThe results of the inverse-variance weighted analysis indicated a causal association between hyperthyroidism and an increased risk of all-cause heart failure (IVW: β=0.048, OR=1.049, 95%CI: [1.013 to 1.087], P=0.007). Similarly, the weighted median approach demonstrated a positive correlation between hyperthyroidism and all-cause heart failure (OR=1.049, [95% CI, 1.001-1.100]; P=0.044). Additionally, no horizontal pleiotropy or heterogeneity was observed. The leave-one-out analysis revealed that the majority of the SNP-driven associations were not influenced by a single genetic marker.ConclusionOur study observed a causal relationship between hyperthyroidism and all-cause heart failure. Hyperthyroidism may associate with heart failure genetically.

Objective: The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays.Methods: Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed in vitro experimentation targeting SNX14 gene expression to confirm whether the variants could alter the expression of SNX14.Results: The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A>T (p.Arg238Ter) and .2744A>T (p.Gln915Leu) in the SNX14 gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the SNX14 c.712A>T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the SNX14 c.2744A>T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A>T (p.Gln915Leu) variant may impact the stability of the SNX14 protein. In vitro experiments demonstrated that both variants reduced SNX14 expression.Conclusion: The SNX14 gene c.712A>T (p.Arg238Ter) and c.2744A>T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and in vitro experimental validation. This discovery expands the range of SNX14 gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children’s families.

Fructose is found in natural foods such as honey and fruits, and it is widely added to processed foods. Globally, the prevalence of hypertension in children is on the rise, high fructose exposure during maternal gestation and lactation can affect blood pressure in the offspring; however, the mechanisms involved are still unclear. Here, We developed a maternal fructose exposure model by feeding 13% and 40% fructose drinking water, performed blood pressure testing on postnatal day 60 offspring. And we used full-length RNA sequencing to identify several terms and pathways associated with blood pressure regulation. In addition, we confirmed that Wnt/β-catenin signaling pathway was activated in the hypothalamus and kidney of the offspring. In conclusion, our results suggested that maternal high fructose exposure during gestation and lactation leads to offspring hypertension and affects blood pressure regulation at the transcriptome level.

Asian shrew moles, genus Uropsilus, are the most primitive members of family Talpidae. They are distributed mainly in southwestern China and adjacent Bhutan, Myanmar, and Vietnam. In June 2022, we collected five specimens of Uropsilus from Mount Huanggang, Jiangxi Province, eastern China, which is the highest peak of the Wuyi Mountains. We sequenced two mitochondrial (CYT B and 12S rRNA) and three nuclear (PLCB4, RAG1, and RAG2) genes to estimate the phylogenetic relationship of the five shrew moles. We also compared their morphology with recognized species within the genus. Our results show that these specimens collected from Mount Huanggang differ from all named species in Uropsilus. We formally describe the species here as Uropsilus huanggangensis sp. nov. Morphologically, the new species is distinguishable from the other Uropsilus species by the combination of dark chocolate-brown pelage, long snout, enlarged first upper incisor, similarly sized lacrimal and infraorbital foramens, and the curved and sickle-like coronoid process. The genetic distances of the cytochrome b (CYT B) gene between U. huanggangensis and other recognized Uropsilus species ranged between 9.3% and 16.4%. The new species is geographically distant from other species in the genus and is the easternmost record of the Uropsilus. The divergence time of U. huanggangensis was estimated to be the late Pliocene (1.92 Ma, 95% CI = 0.88–2.99).

Abstract G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms.

The study aimed to investigate comorbidities, major adverse respiratory events, and mortality in patients with idiopathic pulmonary fibrosis (IPF). We established an IPF cohort and a comparative cohort matched for sex, age, and the date of IPF diagnosis. We recorded the most frequent comorbidities, the proportions, and time durations to the episode of major adverse respiratory events and death. Both cohorts were followed up to the end of 2016. We included 921 patients in the IPF cohort and 3,677 individuals in the comparative cohort. Comorbidities associated with IPF included pulmonary hypertension, chronic obstructive pulmonary disease, heart failure, asthma, and gastroesophageal reflux disease. The IPF cohort was more likely to have pneumonia (47.6 vs 12.0%), acute respiratory failure (17.8 vs 4.30%), chronic respiratory failure (4.23 vs 0.63%), and death (36.3 vs 15.0%) than the comparative cohort. The time durations to the first episode of pneumonia, acute respiratory failure, chronic respiratory failure, and death were 2.09 ± 2.98, 3.12 ± 3.62, 3.20 ± 4.03, and 3.27 ± 3.03 years in the IPF cohort. In conclusion, patients with IPF had significant comorbidities, particularly pulmonary and cardiovascular comorbidities. The duration from diagnosis to the major adverse respiratory events or death was short.

Chordoma is a rare tumor, but has a serious effect on the quality of life of patients. This study aims to assess the overall knowledge structure and trends in the development of chordoma research using a bibliometric analysis and visualization tool. Research datasets were acquired from the Web of Science. VOS viewer and CiteSpace visualization software were used to demonstrate collaborations and correlations. Annual trends in publications, distribution, H‐index status, co‐authorship status, and research hotspots were analyzed. A total of 1844 publications from 2012 to 2022 were included. The number of chordoma‐related publications increased year by year. The United States contributed the most publications (717) and had the highest total citations (10130) and H‐index (50), followed by China. The United States was also the country most frequently involved in international cooperation. The most productive organization involved in chordoma research was Massachusetts General Hospital. World Neurosurgery (114) published the most papers on chordoma. Hornicek FJ was the most productive author over the last decade (41). Initially, diagnosis and the location of onset captured the attention of the research society. Quality of life, risk factors, disability, minimally invasive surgical techniques, molecular targeted therapy, and radiotherapy technology are the research hotspots in recent years. Indeed, this study provides important insights into the overall landscape of chordoma research and also contributes to the further investigation of the international frontier of chordoma.

Alzheimer’s disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

The utilization of optical antennas for active control of far-field radiation at the subwavelength scale is crucial in various scientific and technological applications. We propose a thermally tunable disk design of indium tin oxide (ITO) and aluminum gallium nitride (Al0.18Ga0.82As), enabling a switch between absorption and scattering. Furthermore, the control of far-field radiation pattern can be easily realized by combining ITO and Al0.18Ga0.82As to enhance or suppress emission. Our results demonstrate that hybrid structures can be dynamically tuned with temperature variations. In the proposed design, a frequency is achieved at the wavelength of 1240 nm. The thermal tunability of hybrid structures introduces new multifunctional possibilities for light manipulation, thereby enhancing the potential applications of new devices in the near-infrared range.

BackgroundDopamine, a frequently used therapeutic agent for critically ill patients, has been shown to be implicated in clinical infections recently, however, the precise mechanisms underlying this association remain elusive. Klebsiella quasivariicola, a novel strain belonging to the Klebsiella species, exhibits potential pathogenic attributes. The impact of dopamine on K. quasivariicola infection has aroused our interest.ObjectiveConsidering the contribution of host immune factors during infection, this study aimed to investigate the intricate interactions between K. quasivariicola, dopamine, and macrophages were explored.MethodsRAW264.7 cells and C57/BL6 mice were infected with K. quasivariicola, and the bacterial growth within macrophage, the production of inflammatory cytokines and the pathological changes in mice lungs were detected, in the absence or presence of dopamine. ResultsDopamine inhibited the growth of K. quasivariicola in the medium, but promoted bacterial growth when co-cultured with macrophages. The expression of proinflammatory cytokines increased in RAW 264.7 cells infected with K. quasivariicola, and a significant rise was observed upon the addition of dopamine. The infection of K. quasivariicola in mice induced an inflammatory response and lung injury, which were exacerbated by the administration of dopamine. ConclusionsOur findings suggest that dopamine may be one of the potential risk factors associated with K. quasivariicola infection. This empirical insight provides solid references for clinical precision medicine. Furthermore, an in vitro model of microbes-drugs-host immune cells for inhibitor screening was proposed to more accurately replicate the complex in vivo environment. This fundamental work had contributed to the present understanding of the crosstalk between pathogen, dopamine and host immune cells.

Introduction: Innate and acquired chemoresistance in colorectal cancer (CRC) often results in 5-fluorouracil (5-FU) treatment failure. This study aimed to investigate the potential of Jianpi Jiedu (JPJD) decoction to reverse 5-FU resistance in CRC and clarify its potential mechanism of action. Methods: The CCK-8 assay was employed to assess cell activity. Flow cytometry was employed to assess various parameters including cell apoptosis, cell cycle distribution, P-glycoprotein (P-gp) activity, reactive oxygen species levels, and lipid peroxidation. Metabolomics analysis was conducted to identify differentially expressed metabolites. Western blotting was utilized for protein expression analysis. Results: In this study, we demonstrated that the combined JPJD and 5-FU treatment reversed 5-FU resistance in HCT8/5-FU cells, inducing cell apoptosis, causing G2/M-phase cell cycle arrest, and reducing P-gp protein expression and activity. Metabolomics analysis revealed ferroptosis as a key pathway in the development of 5-FU resistance. Furthermore, the combination treatment reversed drug resistance primarily by impacting ferroptosis and triggering critical ferroptosis events through the suppression of the cystine/glutamate transporter (xCT)/glutathione (GSH)/glutathione peroxidase (GPX4) axis. Conclusion: JPJD decoction primarily suppressed the xCT/GSH/GPX4 axis to trigger ferroptosis, thereby effectively reversing 5-FU resistance in colorectal cancer (CRC).

IntroductionExploring the energy expenditure and substrate metabolism data during exercise, 10-minute recovery, and 20-minute recovery phases in Tabata, HIIT(High-Intensity Interval Training), and MICT(Moderate-Intensity Continuous Training). This study explores the scientific aspects of weight reduction strategies, examining energy expenditure and substrate metabolism from various training perspectives. The aim is to establish a theoretical foundation for tailoring targeted exercise plans for individuals within the population with overweight/obesity.MethodsThis study used an experimental design with fifteen male university students with overweight/obesity. Participants underwent random testing with Tabata, HIIT, and MICT. Tabata involved eight sets of 20 seconds exercise and 10 seconds rest, totaling 4 minutes. HIIT included four sets of power cycling: 3 minutes at 80% VO2max intensity followed by 2 minutes at 20% VO2max. MICT comprised 30 minutes of exercise at 50% VO2max intensity. Gas metabolism indices were continuously measured. Subsequently, fat and glucose oxidation rates, along with energy expenditure, were calculated for each exercise type.ResultsDuring both the exercise and recovery phases, the Tabata group exhibited a significantly higher fat oxidation rate of (0.27 ± 0.03 g/min) compared to the HIIT group (0.20 ± 0.04 g/min, p

Abstract Introduction Whether airway‐compromised airway–esophageal fistula (AEF) patients should undergo combined airway and esophageal stenting is controversial. This study was designed to evaluate the survival prognosis and poststent interventions in AEF patients with airways compromised by advanced malignancy with or without airway stents. Methods A retrospective analysis of the medical records, survival times, and poststent interventions of 17 patients with or without airway stents was performed. Results The causes of AEF were esophageal cancer (11/17, 64.7%), lung cancer (6/17, 29.4%), and thyroid cancer (1/17, 5.9%). All patients received a nasogastric tube (n = 12) or underwent gastrostomy (n = 5) to resume enteral nutrition. Thirteen patients underwent airway stent insertion (13/17, 76.5%), whereas four patients did not. Four patients with a high risk of stent migration received external stent fixation to the trachea. Three of the patients with stents suffered severe granulation tissue formation and needed repeated bronchoscopy interventions. In the stented group, none of the patients developed stent migration, and the overall median survival time was 9 months, compared with 1.25 months in the nonstented group (P = 0.04). Cox proportional hazards regression revealed that stent insertion, nasogastric tube insertion, and transcatheter bronchial artery chemoembolization were protective factors against death, whereas surgery‐related fistula, fistula larger than 2 cm, continued chemotherapy, and age were risk factors for poor survival (P

Vascular dementia (VD) is a prevalent cognitive disorder among the elderly. Its pathological mechanism encompasses neuronal damage, synaptic dysfunction, vascular abnormalities, neuroinflammation, and oxidative stress, among others. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have garnered significant attention as an emerging therapeutic strategy. Current research indicates that MSC-derived extracellular vesicles (MSC-EVs) play a pivotal role in both the diagnosis and treatment of VD. Thus, this article delves into the recent advancements of MSC-EVs in VD, discussing the mechanisms by which EVs influence the pathophysiological processes of VD. These mechanisms form the theoretical foundation for their neuroprotective effect in VD treatment. Additionally, the article highlights the potential applications of EVs in VD diagnosis. In conclusion, MSC-EVs present a promising innovative treatment strategy for VD. With rigorous research and ongoing innovation, this concept can transition into practical clinical treatment, providing more effective options for VD patients.

The rare earth dope d nano-cluster can be a building block for the next-generation photo-electrical industry, so the imminent discovery of novel, suitable nano-functional material is urgent. Praseodymium element as a wonderful dopant, bestow a novel photoelectrochemical properties for nanomaterials especially for semiconductor, derived from its unfulfilled 4f electrons configuration and active electronic transitions between 4f to 4f and 4f to 5d. In view of this, the neutral and anionic clusters of PrSin0/- with a medium size of n = 10–20 are comprehensively investigated by the quantum chemistry method of mPW2PLYP associated with the global searching potential energy surface techniques. The geometry evolution in medium size for PrSin can be attributed to three stages of replaced (n = 10–12), linked (n = 13–19), and cage (n = 20) structure. For PrSin-, two evolution phases are obviously observed by linked (n = 10–19) and cage (n = 20) structure. The PES spectra of the anionic most stable cluster and several degeneracy structures are simulated to identify the ground state structure. Each cluster of AEA, charge transfer, and VDE values are all calculated. Combined with binding energy, HOMO-LUMO gap, molecular orbital analysis, and a series of optical properties estimated, including simulated UV–vis, IR, and Raman spectra, excitation behavior shows PrSi20- has not only prominent stability but also has a proper range of lighting absorption, higher electron-hole recombination, possible as a functional material for optoelectronic devices.