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Abstract Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF‐α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF‐α treatment and miR‐27a‐3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF‐α and decreased level of bone miR‐27a‐3p, and in vitro TNF‐α treatment inhibited miR‐27a‐3p expression in BMSCs. In addition, miR‐27a‐3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red‐S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled‐related protein 1 (Sfrp1) as a downstream target of miR‐27a‐3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF‐α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR‐27a‐3p on the osteogenic differentiation of BMSCs. Furthermore, the miR‐27a‐3p–Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a–β‐catenin signalling. In summary, this study revealed that TNF‐α regulated a novel miR‐27a‐3p–Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.

Abstract Documenting tangible cultural heritage using 3D modeling techniques is gradually becoming an indispensable component of archaeological practice. The 3D modeling techniques based on photogrammetry and LiDAR scanning enable high-accuracy and high-realistic reconstruction of archaeological sites, and have been proven a powerful tool for documenting archaeological excavations. However, dynamically documenting an ongoing excavation using these techniques is still considered tedious, time-consuming, expensive, and dependent on expertise. Moreover, the application of 3D modeling techniques in archaeological excavations still faces some technical challenges, such as modeling with multi-source and multi-scale data, fusing local models at different times into a whole, achieving fast modeling while GPU workstations are not available in the field, and evaluating the quality of 3D models. As a result, there are still very few archaeological teams deeply engaged in dynamic documentation with 3D modeling techniques, and traditional drawing sketches and taking photographs still dominate. In these senses, documenting the archaeological excavation at the Yunxian Man site (located in Hubei, China) is an invaluable opportunity for exploration and practice. Archaeologists determined to conduct dynamically documenting at the beginning of the 6th excavation project for the site, and established a rotation system to reconcile physical excavation with digital preservation. Through repeated practice and communication, we proposed a workflow and pursued several new methods to enhance the feasibility of dynamically documenting, and obtained 4D models of the ongoing archaeological excavations. In 2022, the Yunxian Man site unearthed the most intact fossil of hominin cranium from about one million years ago in the Eurasian continent, preserving important and scarce anatomical features of early humans in Asia. As the original taphonomic context of the fossil corroded away during physical excavations, the digital documentation consisting of 4D models serves as permanent original data source in subsequent archaeological research. Moreover, we obtained cross-scale 3D models from geographical environment to archaeological site, excavation area, and cultural remains, and all of these 3D models are in an actual, unified coordinate framework. Thus, we can contribute to multidisciplinary cross-collaborative research through data sharing. Considering that digital documentations serve a great value in archaeological research, this paper focuses on sharing the workflow and methods to facilitate digital preservation for more archaeological projects.

Abstract Background To identify physical activity (PA) trajectories in adults with or at risk of knee osteoarthritis and to evaluate the association of PA trajectories with incident knee replacement (KR). Methods This study used data from the Osteoarthritis Initiative. The Physical Activity Scale for the Elderly and the KR were assessed annually from baseline to 9 years. Individuals were included if they did not undergo KR surgery at baseline and had data on PA at ≥ 1 visit before KR. Latent class growth mixture Modeling was used to identify the optimal trajectories of PA before KR. Log-binomial regression models were used to assess the association between PA trajectories and the risk of KR. Data analyses were conducted in all individuals and those with radiographic osteoarthritis (ROA) and significant knee pain (Western Ontario and McMaster Osteoarthritis Index pain score of ≥ 5 on a 0–20 scale) at baseline, respectively. Results Of 4731 participants (mean age 61.1 years, 58.5% female), four distinct and slightly declined PA trajectories were identified. Compared to individuals with a “Low” PA trajectory, those with “Medium-low”, “Medium-high”, or “High” PA trajectories were not significantly associated with the risk of KR (risk ratios: 0.97–1.19, all p > 0.05). Similar PA trajectories and associations with the risk of KR were observed in the subgroups of individuals with radiographic osteoarthritis and those with significant knee pain at baseline, respectively. Conclusion In participants with or at risk of knee osteoarthritis, PA slightly declines over time and may play no role in the risk of KR.

To enhance the sensitivity, signal-to-noise ratio and durance of electrospray mass spectrometer, an off-axis ion guide combining a traveling-wave (TW) stacked-ring and a shaped ion funnel has been designed, which is capable of filtering out the neutral contaminants and charged droplets entrained in the electrospray plume. According to its structural characteristics, the corresponding TW and radio frequency (RF) coupling power supply and measurement as well as control system were designed. Customizable Ethernet communication protocol was used to control the field-programmable logic gate array (FPGA) for full-circuit signal control and generation, and an 8-channel traveling-wave amplitude monitoring was achieved through a 12-bit analog-to-digital converter (ADC) and a 16-bit digital-to-analog converter (DAC). In addition, dual-plane transformer coupling circuit was designed. The use of traveling wave changed the central reference frame of the RF, achieving the purpose of programmed RF and the effect of TW in the stacked-ring to provide axial kinetic energy. The stability and accuracy of the electrical parameters of the hardware system on the off-axis transmission structure were tested. The results showed that the controllable voltage range of TW power supply is 0.1-100 V and the controlled DC power supply’s full range detection and control absolute error are less than 0.04 V. The frequency of TW up to 400 kHz, both rising edge and falling edge are less than 30 ns. Furthermore, the waveforms of TW, RF and post-coupling waveform are sufficiently smooth. The test results also showed that the performance of the power supply and measurement and control system are stable and reliable, and their accuracy and range can satisfy the design requirements. Then, the performance of off-axis structure was tested under rough vacuum using reserpine ions. It was found that the reference voltage difference between the upper and lower traveling-waves (the voltage which the ions were extracted), the voltage of the upper traveling-waves, and the traveling-wave duty cycle of the off-axis ion transmitter have more significant effects on the off-axis transmission of ions than other electrical parameters. The experimental results provide a fundamental understanding of ion transport and off-axis separation of traveling-wave stacked-ring structures, which is valuable for the development of high signal-to-noise mass spectrometry system. In the future, this novel traveling-wave off-axis transmitter and its coupling power supply system will be applied to homemade mass spectrometry instruments. Besides, we will compare the developed device with the mainstream ion transmission devices in the market so as to further improve the device structure and power supply parameters, and deeply explore the role of traveling-wave off-axis transmitter in different ionization sources and different detectors.

Abstract Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s−1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching −14.11 mA cm−2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.

This article aimed to establish an amplified luminescent proximity homogeneous assay linked immune sorbent assay (AlphaLISA) for detecting quinolones (QNS) residues in milk. The EDC/NHS active ester method was used to connect 6-aminocaproic acid as the spacer arm on the norfloxacin molecule to prepare biotin-modified norfloxacin hapten (Biotin-6AS-NOR), and QNS monoclonal antibody was coupled on the receptor microsphere. Biotin-6AS-NOR could compete with QNS in the sample to bind quinolone antibodies. A competitive indirect AlphaLISA for QNS residues in milk was established by optimizing the parameters including QNS antibody coupling amount on receptor microspheres, Biotin-6AS-NOR, the dosage of donor/receptor microspheres, and dilution schemes for milk samples. By using the 1:5 milk sample dilution scheme, the limit of detection and the limit of quantification of the established AlphaLISA for QNS in milk were 0.19 ng/mL and 0.46 ng/mL, respectively. The recovery values ranged from 85.97% and 110.11%, and the intraday and interday variation were both less than 10%. The cross-reactivity values for norfloxacin, enrofloxacin, ciprofloxacin, ofloxacin, pefloxacin, ofloxacin, and lomefloxacin were all higher than 70%. In conclusion, the established AlphaLISA showed high sensitivity, accuracy and good repeatability, without the need of tedious wash steps throughout the detection process; therefore, it is easy to achieve automated detection of chemical hazards residue in milk and has high application and promotion value.

Objective Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re‐rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS‐PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. Methods This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS‐PSAT at our institution and were followed up for 8–48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle‐Hindfoot Scale (AOFAS‐AHS), associated with local complications and isokinetic tests. Results None of the patients had infection, necrosis, or sural nerve injury. Re‐rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS‐AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). Conclusion The MIS‐PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re‐rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.

Abstract Background Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study’s aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. Methods Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride–glucose (TyG) index, triglyceride–glucose/body mass index (TyG–BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. Results Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG–BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261–2.000; HR 1.428, 95% CI 1.067–1.910; HR 1.431, 95% CI 1.105–1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. Conclusion Significant associations were found between the TyG index, TyG–BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Abstract Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Highlights Negative charged acidic polarity (NCAP) has been unveiled as the guideline for selecting additives to regulate electric double layer (EDL) for Zn-ion batteries. NCAP glutamate has been verified to regulate EDL structure with synergetic effects, including preferential adsorption on Zn anode and reconstruction of hydrated Zn-ion clusters. Adding NCAP additives, Zn|Cu half-cell achieves a high Coulombic efficiency of 99.83% for 2000 cycles, and NH4V4O10|Zn full cell realizes a high-capacity retention of 82.1% for 3000 cycles.

The H9N2 subtype of avian influenza virus (AIV) is widely prevalent in poultry and wild birds globally, and has become the predominant subtype circulating in poultry in China. The H9N2 AIV can directly or indirectly (by serving as a “donor virus”) infect humans, posing a significant threat to public health. Currently, there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province, central China. In this study, we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province, and genetic analysis revealed that these viruses belonged to 7 different genotypes. Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations, and exhibited diverse replication abilities within these birds. These viruses could replicate efficiently in the lungs of mice, with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys. At the cellular level, the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays, revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level. The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters. Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China. It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.

Abstract The prevalence of non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers, with the Wnt/β-catenin signaling pathway exhibiting robust activation in this particular subtype. The expression of FAM83A (family with sequence similarity 83, member A) has been found to be significantly upregulated in lung cancer, leading to the stabilization of β-catenin and activation of the Wnt signaling pathway. In this study, we conducted a screening of down-regulated miRNAs in lung cancer with FAM83A as the target. Ultimately, we identified miR-1 as a negative regulator of FAM83A and confirmed that FAM83A is a direct target gene of miR-1 through dual luciferase reporter assays. The overexpression of miR-1 significantly attenuated the expression level of FAM83A and suppressed the Wnt signaling pathway, leading to a reduction in the expression levels of downstream target genes AXIN2, CyclinD1, and C-MYC. Additionally, it decreased the nuclear translocation of β-catenin. In addition, overexpression of miR-1 accelerated the degradation of β-catenin by inhibiting FAM83A, promoted the assembly of β-catenin degradation complex, and inhibited the proliferation, migration and invasion of NSCLC cells. In summary, miR-1 may be a potential candidate miRNA for the treatment of NSCLC.

Abstract Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the ‘hotspots’, which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where ‘hotspots’ are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10−14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.

Abstract The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

Abstract We aimed to determine the clinical characteristics of patient self-inflicted lung injury (P-SILI)-associated pneumothorax/pneumomediastinum, to reveal its risk factors, and to assess its impact on severe COVID-19 cases. In total, 229 patients were included in this case-control study. They were randomly divided into either the case group or the control group as per the inclusion and exclusion criteria. The two groups were further analyzed to reveal the risk factors of spontaneous pneumothorax/pneumomediastinum (SP/P). Finally, risk factors for death were analyzed in the case group and the relationship between death and SP/P was also analyzed among all patients. The mean age of patients was 59.69 ± 17.01 years, most of them were male (74.2%), and 62.0% of them had comorbidities upon admission. A respiratory rate higher than 30 BPM was a risk factor for SP/P (OR 7.186, 95% CI 2.414–21.391, P

To evaluate the effects of dietary supplementation with succinic acid on growth performance, flesh quality, glucose, and lipid metabolism of Nile tilapia (Oreochromis niloticus) fed a high-carbohydrate diet (HCD), five iso-nitrogenous and iso-lipidic diets were prepared as follows: HCD (control group) consisting of 55% corn starch and HCD supplemented with 0.5%, 1.0%, 2.0%, and 4.0% succinic acid, respectively. Tilapia with an initial body weight of 204.90 ± 1.23 g randomly assigned to 15 tanks with 3 replicates per group and 10 fish per tank fed for 8 weeks. Increasing dietary succinic acid supplementation resulted in significant second-order polynomial relationship in the weight gain rate (WGR), specific growth rate (SGR), feed conversion ratio (FCR), protein efficiency rate (PER), viscerosomatic index, condition factor, and contents of muscular crude lipid and glycogen (P

There are only eight approved small molecule antiviral drugs for treating COVID-19. Among them, four are nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other four are protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, and simnotrelvir-ritonavir). Antiviral resistance, unfavourable drug‒drug interaction, and toxicity have been reported in previous studies. Thus there is a dearth of new treatment options for SARS-CoV-2. In this work, a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 activity. One compound, designated 172, demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of concern. Mechanistic studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease (3CLpro) by binding to an allosteric site and reduces 3CLpro dimerization. A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in vitro. In vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 mice. Overall, this study identified an alternative druggable site on the SARS-CoV-2 3CLpro, proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

Abstract Background Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown. Methods We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student’s t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0. Results We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice. Conclusions The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection. Graphical Abstract

Abstract Underground cavities have complex spatial structures and geological settings, their arrangement is dense and crisscrossed. The construction system involves multiple work surfaces, levels, and processes. The close integration of construction simulation with actual production conditions is crucial for enhancing the guidance that simulation results provide for practical engineering. Therefore, from the perspective of optimizing construction organization and management, this article comprehensively considers various factors in the construction process, innovatively introduces the principle of production line balance and the concept of rule cycle, and combines technology and management, an underground cavities construction simulation system (UCCSS) is developed. In UCCSS, a hierarchical model is built and calculation are performed on models with different construction methods by modifying the parameters as per the actual engineering characteristics. The simulation results are comprehensively analysed to determine the optimal construction programme. An application case is proposed based on the construction organisation design of the long and parallel diversion tunnels at the CB Hydropower Station. The results show that the system has good practicality and credibility and can provide guidance for the construction organisation design of underground cavities with various features.

Abstract In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority 3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Abstract Metal-oxide interfaces with poor coherency have specific properties comparing to bulk materials and offer broad applications in heterogeneous catalysis, battery, and electronics. However, current understanding of the three-dimensional (3D) atomic metal-oxide interfaces remains limited because of their inherent structural complexity and the limitations of conventional two-dimensional imaging techniques. Here, we determine the 3D atomic structure of metal-oxide interfaces in zirconium-zirconia nanoparticles using atomic-resolution electron tomography. We quantitatively analyze the atomic concentration and the degree of oxidation, and find the coherency and translational symmetry of the interfaces are broken. Atoms at the interface have low structural ordering, low coordination, and elongated bond length. Moreover, we observe porous structures such as Zr vacancies and nano-pores, and investigate their distribution. Our findings provide a clear 3D atomic picture of metal-oxide interface with direct experimental evidence. We anticipate this work could encourage future studies on fundamental problems of oxides, such as interfacial structures in semiconductor and atomic motion during oxidation process.

Abstract Immunotherapy has shown promising anti-tumor effects across various tumors, yet it encounters challenges from the inhibitory tumor immune microenvironment (TIME). Infiltrating regulatory T cells (Tregs) are important contributors to immunosuppressive TIME, limiting tumor immunosurveillance and blocking effective anti-tumor immune responses. Although depletion or inhibition of systemic Tregs enhances the anti-tumor immunity, autoimmune sequelae have diminished expectations for the approach. Herein, we summarize emerging strategies, specifically targeting tumor-infiltrating (TI)-Tregs, that elevate the capacity of organisms to resist tumors by reprogramming their phenotype. The regulatory mechanisms of Treg reprogramming are also discussed as well as how this knowledge could be utilized to develop novel and effective cancer immunotherapies.

Abstract Background Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family’s largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria’s taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system. Results This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK–rps16, trnC–petN, petN–psbM, accD–psaI, petA–psbJ, rpl32–trnL, ccsA–ndhD, rps15–ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics. Conclusions The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.

Abstract Primary central nervous system lymphoma (PCNSL) is a rare and frequently fatal lymphoma subtype. The programmed death-1 (PD-1) pathway has emerged as a potential therapeutic target, but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined. In this phase 2 trial (ChiCTR1900027433) with a safety run-in, we included patients aged 18–70 with newly diagnosed PCNSL. Participants underwent six 21-day cycles of a SMTR regimen, which includes sintilimab (200 mg, Day 0), rituximab (375 mg/m2, Day 0), methotrexate (3.0 g/m2, Day 1 or 1.0 g/m2 for patients aged ≥65 years), and temozolomide (150 mg/m2/d, Days 1–5). Among 27 evaluable patients, the overall response rate (ORR) was 96.3% (95% confidence interval: 81–99.9%), with 25 complete responses. At a median follow-up of 24.4 months, the medians for duration of response, progression-free survival (PFS), and overall survival were not reached. The most common grade 3–4 treatment-related toxicities were increased levels of alanine aminotransferase (17.9%) and aspartate aminotransferase (14.3%). Additionally, baseline levels of interferon-α and the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS, achieving areas under the curve of 0.88 and 0.84, respectively, at 2 years. Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group, while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group. These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL, warranting further investigation.

Abstract Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

Abstract This study investigates the potential anti-colorectal cancer (CRC) activity of IMT1, a novel specific inhibitor of mitochondrial RNA polymerase (POLRMT). Single-cell RNA sequencing data reveal that POLRMT is overexpressed in CRC cells. Additionally, elevated POLRMT expression was observed in local CRC tissues and cells, while its expression remained relatively low in colon epithelial tissues and cells. IMT1 significantly inhibited colony formation, cell viability, proliferation, cell cycle progression, and migration in both primary and immortalized CRC cells. Furthermore, IMT1 induced apoptosis and cell death in CRC cells. The inhibition of POLRMT by IMT1 disrupted mitochondrial functions in CRC cells, leading to mitochondrial depolarization, oxidative damage, and decreased ATP levels. Using targeted shRNA to silence POLRMT closely mirrored the effects of IMT1, showing robust anti-CRC cell activity. Crucially, the efficacy of IMT1 was diminished in CRC cells with silenced POLRMT. Contrarily, boosting POLRMT expression externally by a lentiviral construct promoted the proliferation and migration of CRC cells. Importantly, treatment with IMT1 or silencing POLRMT in primary colon cancer cells decreased the phosphorylation of Akt1-S6K1, whereas overexpression of POLRMT had the opposite effect. In nude mice, orally administering IMT1 potently restrained primary colon cancer xenograft growth. IMT1 suppressed POLRMT activity, disrupted mitochondrial function, hindered Akt-mTOR activation, and prompted apoptosis within the xenograft tissues. In addition, IMT1 administration suppressed lung metastasis of primary colon cancer cells in nude mice. These combined results highlight the robust anti-CRC activity of IMT1 by specifically targeting POLRMT.

Abstract Studies have indicated that RAB17 expression levels are associated with tumor malignancy, and RAB17 is more highly expressed in endometrial cancer (EC) tissues than in peritumoral tissues. However, the roles and potential mechanisms of RAB17 in EC remain undefined. The present study confirmed that the expression of RAB17 facilitates EC progression by suppressing cellular ferroptosis-like alterations. Mechanistically, RAB17 attenuated ferroptosis in EC cells by inhibiting transferrin receptor (TFRC) protein expression in a ubiquitin proteasome-dependent manner. Because EC is a blood-deprived tumor with a poor energy supply, the relationship between RAB17 and hypoglycemia was investigated. RAB17 expression was increased in EC cells incubated in low-glucose medium. Moreover, low-glucose medium limited EC cell ferroptosis and promoted EC progression through the RAB17-TFRC axis. The in vitro results were corroborated by in vivo studies and clinical data. Overall, the present study revealed that increased RAB17 promotes the survival of EC cells during glucose deprivation by inhibiting the onset of TFRC-dependent ferroptosis.

Abstract Paired immunoglobin-like type 2 receptor beta (PILRB) mainly plays a crucial role in regulating innate immunity, but whether PILRB is involved in cancer is poorly understood. Here, we report that PILRB potentiates the PI3K/AKT pathway to drive gastric tumorigenesis by binding and stabilizing IRS4, which could hyperactivate the PI3K/AKT pathway. Firstly, the levels of PILRB are upregulated in human gastric cancer (GC) specimens and associated with poor prognosis in patients with GC. In addition, our data show that PILRB promotes cell proliferation, colony formation, cell migration and invasion in GC cells in vitro and in vivo. Mechanistically, PILRB recruits the deubiquitination enzymes OTUB1 to IRS4 and relieves K48-linked ubiquitination of IRS4, protecting IRS4 protein from proteasomal-mediated degradation and subsequent activation of the PI3K/AKT pathway. Importantly, the levels of PILRB are positively correlated with IRS4 in GC specimens. Meanwhile, we also found that PILRB reprogrammed cholesterol metabolism by altering ABCA1 and SCARB1 expression levels, and PILRB-expression confers GC cell resistance to statin treatment. Taken together, our findings illustrate that the oncogenic role of PILRB in gastric tumorigenesis, providing new insights into the regulation of PI3K/AKT signaling in GC and establishing PILRB as a biomarker for simvastatin therapy resistance in GC.

Abstract Background Nonrestorative sleep (NRS) is related to numerous adverse outcomes. There is rare evidence of its associated factors, especially in Chinese adolescents. This study aimed to explore the factors associated with NRS in Chinese adolescents and the potential moderation effects of coffee or tea consumption. Methods This cross-sectional study invited adolescents attending Grades 7–11 in Nanjing, China, to complete a self-administered questionnaire, including their NRS, stress, anxiety, physical symptoms, depression, sociodemographics, and lifestyles. Linear regressions were applied to investigate the associated factors of their NRS, with the moderation effects of coffee or tea consumption and other characteristics being tested by additionally including their interactions. Results Totally 481 adolescents (49% male, age 15.5 ± 1.5 years) were enrolled, with the average global NRS score of 42.16 ± 7.57. Higher family income (β = 2.01, P = 0.007), longer sleep duration (β = 2.33, P = 0.011), and moderate after-class activity (β = 1.50, P = 0.044) contributed less NRS, while higher educational level (β = −2.60, P = 0.033), more coffee or tea consumption (β = −1.68, P = 0.013), physical symptoms (β = −3.85, P

Abstract Background HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. Methods The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014–2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018–2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. Results The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P

Hui Tang,1 Xiurong Xing,1 Yingna Han,1 Daiquan Gao,2 Piu Chan,3 Shengfang Zhang,4 Huixin Xue4 1Department of Emergency Internal Medicine, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurobiology, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 4School of Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hui Tang, Department of Emergency Internal Medicine, Xuanwu Hospital of China Capital Medical University, No. 45 of Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-1083198280, Email tanghui_202186@21cn.comObjective: To investigate the clinical characteristics, risk factors and outcomes of brain-heart syndrome (BHS) in patients with acute cerebrovascular diseases (ACVDs).Methods: A retrospective analysis was conducted of 100 patients who were admitted to our hospital with ACVDs between January 2023 and December 2023. The demographic, clinical, laboratory and imaging data of the patients were collected, and the presence and severity of BHS were evaluated. The neurological and cardiac outcomes of the patients at discharge and at 12-month follow-up were also assessed.Results: Out of the 100 patients, 38% had BHS, classified as mild (18%), moderate (12%) and severe (8%). The most prevalent ACVDs were cerebral infarction (58%), cerebral haemorrhage (32%) and subarachnoid haemorrhage (10%). Cardiac complications included arrhythmia (26%), myocardial ischaemia (18%) and heart failure (10%). Patients with BHS had higher results for blood pressure, heart rate, white blood cell count, C-reactive protein, IL-6, D-dimer and troponin, more severe neurological deficits, higher mortality and poorer functional outcomes. Multivariable analysis identified age, hypertension, diabetes, coronary artery disease, prior cardiovascular events, cerebral haemorrhage, brainstem infarction and hypothalamic or insular lesions as independent risk factors for BHS.Conclusion: Brain-heart syndrome is a frequent, severe complication in patients with ACVD, linked with multiple risk factors and poor prognosis. Prompt diagnosis and treatment are crucial for improving patient outcomes.Keywords: brain-heart syndrome, acute cerebrovascular diseases, cerebral infarction, cerebral haemorrhage

Background: Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone. Methods: Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research). Results: Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis. Conclusion: During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.The translational potential of this article is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.

Bing Yu,1,* Zhimei Xing,2,* Xiaoxuan Tian,2 Rui Feng1 1Department of Breast Surgery, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, People’s Republic of China; 2State Key Laboratory of Component‑Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Feng, Department of Breast Surgery, Tianjin Central Hospital of Obstetrics and Gynecology, No. 156 of Nankai SAN Road, Nankai District, Tianjin, 300100, People’s Republic of China, Tel +86 022-58287167, Email dr.fr@126.comBackground: Triple-negative breast cancer (TNBC) is recognized as the most aggressive molecular subtype of breast cancer. Recent studies have highlighted the complex role of autophagy in the pathogenesis of TNBC.Methods: In this study, we evaluated 18,330 genes, including 1111 autophagy-related genes, (ARGs), across 579 TNBC samples from online databases. Differentially expressed ARGs in TNBC were identified using high-throughput RNA-seq data from the Cancer Genome Atlas (TCGA). Prognostic factors were examined through Cox regression and multivariate Cox analyses, with predictive efficacy assessed using receiver operating characteristic (ROC) curves. A nomogram integrating the risk signature with clinicopathological factors, such as TNM stage, was developed. Immunohistochemical analysis of clinical samples was also conducted.Results: EIF4EBP1 and NPAS3 were significantly correlated with prognostic outcomes in patients with TNBC. Multivariate Cox regression analysis demonstrated that the expression levels of these two genes were accurate predictors of disease progression in TNBC samples from TCGA and the GSE31519 dataset. The efficacy of this predictive model was validated using ROC curve analysis and calibration plots, confirming its ability to accurately estimate the 1-, 2-, and 3-year survival rates for individuals with TNBC. Additionally, EIF4EBP1 and NPAS3 expression influenced drug sensitivity in TNBC cell lines, with notably lower NPAS3 expression in TNBC tissues, particularly in Stage III cases. This study is the first to report NPAS3 expression in patients with TNBC.Conclusion: The autophagy-related genes EIF4EBP1 and NPAS3 may serve as independent prognostic factors for individuals with TNBC.Keywords: autophagy, nomogram, prognosis, risk signature, triple-negative breast cancer

Qian Yuan,* Long-Wu Xiao,* Yao Zhang, Long Li, Teng Xia, Qing Xu, Shi-Gui Xing, Liu-Shun Wang Department of Thoracic Surgery, Nan Jing Gaochun PEople’s Hospital (The Gaochun Affiliated Hospital of Jiang Su University), Nanjing, Jiangsu, 210000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Gui Xing; Liu-Shun Wang, Email gcxw5988@163.com; lswang052066@sina.comBackground: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline.Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships.Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(β, − 23.4061; 95% CI, − 42.2805- − 4.5317), FEV1(β, − 46.7730; 95% CI, − 63.3371- − 30.2089), FEV1%(β, − 0.7923; 95% CI, − 1.1635- − 0.4211), FEV1/FVC(β, − 0.6366; 95% CI, − 0.8328- − 0.4404) and PEF(β, − 121.4468; 95% CI,-164.1939- − 78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly.Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.Keywords: NHANES, population-based study, systemic immune-inflammation index, pulmonary function

Aiming at the issues of ant colony algorithm in solving large-scale traveling salesman problems (TSP), such as easily falling into local optima and slow convergence speed, an ant colony algorithm integrating adaptive clustering and mother ant guidance strategy (AMACS) is proposed. In the adaptive clustering process, firstly, an improved clustering method is used, which leverages the concepts of maximum-minimum distance and class density to obtain the optimal clustering results through an adaptive clustering strategy, and quickly obtains the optimized solution for each cluster. Next, the neighboring clusters are fused using a spider web fusion principle, effectively enhancing the accuracy of the initial solution. Additionally, the initial solution is optimized through the mother ant guidance strategy, which includes two components: path guidance and pheromone optimization. Path guidance sets the initial solution as the solution for the first generation, improving the stability of the algorithm; pheromone optimization involves stimulating the pheromone along the initial solution’s path, thereby enhancing the solution’s accuracy. Finally, a random recombination strategy is employed to reorganize and randomly stimulate the pheromones, helping the algorithm to escape local optima and improving the solution’s accuracy. Experimental results show that the proposed algorithm not only ensures solution accuracy when solving large-scale TSPs but also improves the stability of the algorithm.

Abstract Converting solar energy into fuels is pursued as an attractive route to reduce dependence on fossil fuel. In this context, photothermal catalysis is a very promising approach through converting photons into heat to drive catalytic reactions. There are mainly three key factors that govern the photothermal catalysis performance: maximized solar absorption, minimized thermal emission and excellent catalytic property of catalyst. However, the previous research has focused on improving solar absorption and catalytic performance of catalyst, largely neglected the optimization of thermal emission. Here, we demonstrate an optically selective catalyst based Ti3C2Tx Janus design, that enables minimized thermal emission, maximized solar absorption and good catalytic activity simultaneously, thereby achieving excellent photothermal catalytic performance. When applied to Sabatier reaction and reverse water-gas shift (RWGS) as demonstrations, we obtain an approximately 300% increase in catalytic yield through reducing the thermal emission of catalyst by ~70% under the same irradiation intensity. It is worth noting that the CO2 methanation yield reaches 3317.2 mmol gRu −1 h−1 at light power of 2 W cm−2, setting a performance record among catalysts without active supports. We expect that this design opens up a new pathway for the development of high-performance photothermal catalysts.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Recent studies have shown that age-related aging evolution is accompanied by imbalances in intestinal homeostasis. Marine red yeast (MRY) is a functional probiotic that has been shown to have antioxidant, immune and other properties. Therefore, we chose 900 healthy Hy-Line Brown hens at 433 d old as the research subjects and evaluated the correlation between intestinal health, laying performance, and egg quality in aged hens through the supplementation of MRY. These laying hens were assigned into 5 groups and received diet supplementation with 0%, 0.5%, 1.0%, 1.5%, and 2% MRY for 12 weeks. The results showed that MRY supplementation increased egg production rate, average egg weight, and egg quality, and decreased feed conversion ratio and daily feed intake (P

The high-temperature molten salt pump is the core equipment in the small modular molten salt reactor with media temperatures up to 700 °C. The cantilever ratio of the molten salt pump is usually large. Excessively large cantilever ratios cause increased deformations and rotational amplitudes at the impeller, thus affecting the operational stability of the main pump; small cantilever ratios cause heavy temperature gradients, thus affecting the structural integrity evaluation. This paper used numerical simulation methods to calculate and analyze the temperature field, stress, and structural integrity, optimized the pump shaft cantilever length of the original scheme based on structural integrity using the dichotomy method, and analyzed the rotor dynamics of the optimization results. The results of this study show that the thermal expansion load caused by the temperature difference has a significant mechanical effect on the structure; the first-order critical speed of the rotor system of the optimized schemes has been improved, and the amplitude of the unbalanced response has been significantly reduced, which not only improves the operational stability of the rotor, also contributes to the compact design of the main pump of a small modular molten salt reactor.

Introduction: Global warming is increasing interest in how aquatic animals can adjust their physiological performance and cope with temperature changes. Therefore, understanding the behavioral changes and molecular underpinnings in fish under warming is crucial for both the individual and groups survival. This could provide experimental evidence and resource for evaluating the impact of global warming. Objective: Three genetic families of common carp (Cyprinus carpio) were generated. These juveniles were constructed short-term (4 days) and long-term (30 days) warming groups to investigate the effects of warming on behavioral responses and to elucidate the potential underlying mechanisms of warming-driven behavior. Methods: Behavioral tests were used to explore the effects of short- and long-term exposure to warming on the swimming behavior of C. carpio. Brain transcriptome combined with measurement of nervous system activity was used to further investigated the comprehensive neuromolecular mechanisms under warming. Results: Long-term warming groups had a more significant impact on the decline of swimming behavior in juvenile C. carpio. Furthermore, brain comparative transcriptomic analysis combined with measurement of nervous system activity revealed that genes involved in cytoskeletal organization, mitochondrial regulation, and energy metabolism are major regulators of behavior in the juvenile under warming. Importantly, especially in the long-term warming groups, enrichment analysis of associated gene expression suggested functional alterations of synaptic transmission and signal transduction leading to swimming function impairment in the central nervous system, as revealed by behavioral tests. Conclusions: Our study provides evidence of the neurogenomic mechanism underlying the decreased swimming activity in juvenile C. carpio under warming. These findings have important implications for understanding the impacts of climate change on aquatic ecosystems and the organisms that inhabit them.

This study investigates the hot compression behavior of a molybdenum- Rhenium (Mo–Re) alloy, focusing on deformation mechanisms and instability. Utilizing electron backscattered diffraction (EBSD) and transmission electron microscope (TEM), we characterized the microstructure, grain orientation, and deformation behavior across temperatures (650, 750, 850, and 950 °C) and strain rates (0.01, 0.1, 1, and 10s-1). The study reveals that Mo–Re alloys exhibit high hot deformation resistance, necessitating optimal processing conditions for effective plastic deformation. Key findings by EBSD and TEM include the formation of dislocation networks and substructures enhancing grain plasticity. We established a constitutive equation and processing maps, providing valuable insights for industrial applications and future alloy development.

ABSTRACT: Buffaloes are vital contributors to the global dairy industry. Understanding the genetic basis of milk production traits in buffalo populations is essential for breeding programs and improving productivity. In this study, we conducted whole-genome resequencing on 387 buffalo genomes from 29 diverse Asian breeds, including 132 river buffaloes, 129 swamp buffaloes, and 126 crossbred buffaloes. We identified 36,548 copy number variants (CNV) spanning 133.29 Mb of the buffalo genome, resulting in 2,100 CNV regions (CNVR), with 1,993 shared CNVR being found within the studied buffalo types. Analyzing CNVR highlighted distinct genetic differentiation between river and swamp buffalo subspecies, verified by evolutionary tree and principal component analyses. Admixture analysis grouped buffaloes into river and swamp categories, with crossbred buffaloes displaying mixed ancestry. To identify candidate genes associated with milk production traits, we employed 3 approaches. First, we used Vst-based population differentiation, revealing 11 genes within CNVR that exhibited significant divergence between different buffalo breeds, including genes linked to milk production traits. Second, expression quantitative loci analysis revealed differentially expressed CNVR-derived genes (DECG) associated with milk production traits. Notably, known milk production-related genes were among these DECG, validating their relevance. Last, a GWAS identified 3 CNVR significantly linked to peak milk yield. Our study provides comprehensive genomic insights into buffalo populations and identifies candidate genes associated with milk production traits. These findings facilitate genetic breeding programs aimed at increasing milk yield and improving quality in this economically important livestock species.

Most of the literature on reviewer assignment problem (RAP) considers fitness or efficiency as the evaluation criterion of an assignment, e.g., the degree of matching between reviewers and proposals. In this study, we consider fairness of an assignment and establish two multi-objective linear integer programming models for proposal assignment. We introduce a definition of fairness based on the closeness of social relationships between scholars. The closeness of social relationships is quantified based on social networks among reviewers and serves as part of objective functions. An improved space-partitioning algorithm is designed to solve the multi-objective models with integer objectives. When the problem size is large, two meta-heuristic algorithms are applied. Experiments on real and randomly generated cases are provided to illustrate the effectiveness of the proposed models and algorithms.

Myasthenia gravis(MG) is an autoimmune disease mainly mediated by autoantibodies that disorders the transmission of excitation at the neuromuscular junction. The predominant clinical manifestation is the muscle fluctuant weakness and fatigability, and the extraocular and skeletal muscles are slightly affected at the early onset for the majority of MG patients. However, there is a rapid progression in a short period of time for a small group, involving the laryngeal muscles and respiratory muscles and developing the myasthenia crisis, which severely threatens their lives. It’s commonly used for such patients to be rescued by therapeutic plasma exchange(TPE) or intravenous immunoglobulins(IVIG) that rapidly relieves their symptoms of muscle weakness and improves the respiratory function. In recent years, plentiful clinical studies about TPE have emerged, and the clinical value of TPE in improving MG symptoms, exerting early efficacy, reducing the length of ICU hospital stay and its safety has been gradually clarified. This review aims to summarize the clinical research advancement of TPE in the treatment of MG in terms of basic conditions of MG and TPE, the therapeutic efficiency and safety of TPE, and the application of TPE extension technology in the treatment of MG by searching for clinical research articles at home and abroad in the past 5 years, which can provide reference for better clinical application of MG.

To meet the “peak carbon and carbon neutrality” targets, the gradual reduction of coal-fired electricity generation through the co-firing of coal and NH3 has emerged as a new pathway to achieve carbon reduction. However, the co-firing characteristics of coal and NH3 are not yet clear. Therefore, the coal/NH3 co-firing experiments were conducted based on a flat-flame burner to investigate the influence of ammonia blending ratio (E(NH3), 0−100%) and coal/NH3 injection methods (pre-mixed, non-pre-mixed) on combustion characteristics. Camera, flue gas analyzer, and thermocouples were used to observe flame morphology, gas composition, temperature distribution along the centerline heights above the burner (HAB), and measure the unburned carbon content in fly ash. The results showed that during the initial stage of combustion, the competition for O2 between coal and NH3 was more pronounced. The NH3 combustion in the combustion zone created a rich water vapor atmosphere. Under low E(NH3) conditions in pre-mixed combustion, CO reacted with OH, resulting in a decrease in CO concentration. On the other hand, under high E(NH3) conditions, NH3 preferentially reacted with O2, leading to an incomplete combustion of a significant amount of carbon. Additionally, the rich water vapor atmosphere promoted coal gasification reactions, resulting in a significant increase in CO concentration in the combustion reduction zone, reaching a maximum of 19773.05 mg/Nm3. However, this process altered the pore structure of the coke, increased the specific surface area of the coke, accelerated the combustion process of coal powder, and reduced the residual carbon content in fly ash from 13.90% (pure coal combustion) to 13.44% (E(NH3)=80%) under pre-mixed conditions. An early injection of NH3 reduced the preheating effect of NH3 combustion on coal powder and decreased the combustion intensity in the flame reaction zone. The addition of NH3 significantly increased the NOx emissions, and with increasing E(NH3), there was an initial increase followed by a decrease in NOx, with the peak concentration of NO occurring earlier. The unburned NH3 content and oxygen content were the main factors influencing the formation of N2O and NO2. Increasing the residence time of coal/NH3 combustion, reducing the unburned NH3 content, and creating a reducing atmosphere were effective ways to reduce NOx emissions. Under high E(NH3) conditions in pre-mixed combustion (E(NH3)≥80%, HAB=100 mm) and non-pre-mixed conditions, the CO2 percentage showed a decreasing trend with increasing E(NH3). Pre-mixed conditions with an E(NH3) range of 40% to 60% were more favorable for achieving low nitrogen, low carbon, and high-efficiency combustion of coal/NH3. The co-firing of coal powder with NH3 exhibited mutual promotion and restriction effects, requiring some effective measures based on specific circumstances to harness the promotion effect of coal/NH3 co-firing.

Cerium oxide nanoparticles (CeO2 NPs), as the oxides of the most abundant elements in rare earths, have been widely used in biomedical and industrial production and other fields that are closely related to human life. China is a large country in resources and production of rare earth, and the impact of CeO2 NPs on human health has been increasingly concerned. In response to the possible health risks of CeO2 NPs, researchers begin to focus on their toxic effects on living organisms, especially on the reproductive system. The male reproductive system is not only responsible for producing sperm and regulating the secretion of testosterone, but also plays a key role in maintaining male sexual characters and function. Any adverse effects on the male reproductive system may lead to reduced fertility and reproductive dysfunction. Some studies have shown that long-term exposure to CeO2 NPs may lead to gonadal damage, sex hormone disorders, and other problems in male animals. Therefore, an in-depth study of the potential effects of CeO2 NPs on the male reproductive system is of great scientific significance and practical value. In this study, we reviewed the male reproductive toxicity of CeO2 NPs in terms of spermatogenic cells, spermatozoa structure, blood-testis barrier, hypothalamic-pituitary-gonadal axis, and functional changes in epididymis, and analyzed the effects of the size and shape of physicochemical parameters of CeO2 NPs on the toxicity to male reproductive system. The findings will provide a theoretical basis and scientific evidence for the rational use of CeO2 NPs.

Background: Benign prostate hyperplasia (BPH) occurs in elder men globally with high prevalence. Human diet and lifestyle aroused great attention in the prevalence of BPH. Prostate enlargement (PE) is a major symptom of BPH. Objectives: To elaborate the effect of total diet quality for adults from the United States, we investigated the association between Health Eating Index (HEI)-2015 and the risk of PE in adults from the National Health and Nutrition Examination Survey (NHANES). Methods: This cross-sectional study was conducted based on NHANES 2001–2008. Participants who reported a PE history were included. We conducted a logistic regression analysis to investigate the association between HEI-2015 and PE. Results: A total of 4,866 male participants aged 40 and above were enrolled. Compared with Q1 of HEI-2015, no significant differences were found in adjusted models. Higher vegetables intake (Odds ratio [OR] = 1.073; 95% confidence interval [95%CI] 1.015 to 1.134, P = 0.02) and higher total dairy intake (OR = 1.034; 95%CI 1.009 to 1.061, P = 0.01) were significantly related with higher risk of PE. Conclusions: There was no significant difference between HEI-2015 and PE after full adjustment. Total vegetables and dairy product might be associated with higher risk of PE and needed further validation.

Hepatocellular carcinoma (HCC) is among the most common malignant liver tumors. Despite progress in anticancer drugs and surgical approaches, early detection of HCC remains challenging, often leading to late-stage diagnosis where rapid disease progression precludes surgical intervention, leaving chemotherapy as the only option. However, the systemic toxicity, low bioavailability, and significant adverse effects of chemotherapy drugs often lead to resistance, rendering treatments ineffective for many patients. This article outlines how nanoparticles, following functional modification, offer high sensitivity, reduced drug toxicity, and extended duration of action, enabling precise targeting of drugs to HCC tissues. Combined with other therapeutic modalities and imaging techniques, this significantly enhances the diagnosis, treatment, and long-term prognosis of HCC. The advent of nanomedicine provides new methodologies and strategies for the precise diagnosis and integrated treatment of HCC.

Abstract Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts.