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Non-local metasurface supporting geometric phases at bound states in the continuum (BIC) simultaneously enables sharp spectral resonances and spatial wavefront shaping, thus providing a diversified optical platform for multifunctional devices. However, a static nonlocal metasurface cannot manipulate multiple degrees of freedom (DOFs), making it difficult to achieve multifunctional integration and be applied in different scenarios. Here, we presented and demonstrated phase-change non-local metasurfaces that can realize dynamic manipulation of multiple DOFs including resonant frequency, Q values, band, and spatial wavefront. Accordingly, a metasurface integrating multiple distinct functions is designed, as a proof-of-concept demonstration. Utilizing the geometry phase of quasi-BIC and the tunability of vanadium dioxide (VO2), a dynamic meta-lens is achieved by tailoring spatial light response at quasi-BIC in the temperature range from room temperature to 53 °C. Simultaneously, the sharp Fano resonance of quasi-BIC enables the metasurface to serve as an optical sensor in the mid-infrared band, yielding a sensitivity of 7.96 THz/RIU at room temperature. Furthermore, at the metallic state of VO2 (80 °C), the designed metasurface converts into a mid-infrared broadband absorber, achieving higher than 80 % absorptivity and an average absorption of 90 % from 28.62 THz to 37.56 THz. The proposed metasurface enabling multifunctional performances in different temperatures can effectively improve the availability of devices and find more new and complex scenarios in sensing, imaging, and communications.

Pores are among the primary defects in 316L stainless steel when fabricated through laser powder bed fusion (L-PBF). To better understand and precisely control the formation behavior of pores in the L-PBF-manufactured 316L stainless steel, effects of L-PBF process parameters on the melt pool and pore characteristics have been investigated. A method utilized for extreme values statistics analysis was also applied to investigate and predict the sizes of pores. Relationships among the count of measurements, the laser energy density, the reduced variate, and the maximum pore size were revealed. The findings showed an overall increase in melt pool depth as the laser energy densities was raised, yet the magnitude of this growth weakened as the laser energy density continued to increase. Conversely, it was discovered that the connection between the width of the melt pool and the density of laser energy exhibited a markedly less distinct correlation. As laser energy density escalated, there was a shift in the melt pool mode from conduction-based to a transitional phase, and upon further elevation of the laser energy density, it transitioned to keyhole mode. To obtain a reliable statistical analysis of pores, at least 40 measurements should be acquired for the estimation of the pore sizes by taking comprehensive consideration of time cost. Beside, in all three melt pool modes, at a fixed observation area, the maximum size of pores generally decreased with the escalation in laser energy densities.

As an alloying element in steel, manganese can considerably enhance the mechanical properties of structural steel. However, the Mn volatilisation loss in vacuum melting is severe because of the high saturated vapour pressure, resulting in an unstable Mn yield and Mn content fluctuation. Therefore, a systematic study of the volatilisation behaviour of Mn in vacuum melting is required to obtain a suitable Mn control process to achieve precise control of Mn composition, thereby providing a theoretical basis for industrial melting of high-Mn steel. In order to explore the Mn volatilization behavior, the volatilization thermodynamics and volatilisation rate of Mn, as well as the influence factors are discussed in this study. The results shows that Mn is extremely volatilised into the vapour phase under vacuum, the equilibrium partial pressure is closely related to Mn content and temperature. With an increase in the Mn content, a higher C content has a more obvious inhibitory effect on the equilibrium partial pressure of Mn. The maximum theoretical volatilisation rate of Mn shows a linear upward trend with an increase in Mn content. However, a higher C content has a more obvious effect on the reduction of the maximum theoretical volatilisation rate with the increase of Mn content. This study provides an improved understanding of Mn volatilisation behaviour as well as a theoretical foundation for consistent Mn yield control during the vacuum melting process of high-Mn steel.

Objectives This cross-sectional study aimed to explore the knowledge, attitude and practice (KAP) of patients with rotator cuff tears towards arthroscopic shoulder surgery (ASS), based on the hypothesis that the knowledge of the procedure among patients would be sufficient, which in turn might influence their practice and attitude.Design Cross-sectional study.Setting Patients were recruited from Tong Ren Hospital between September and October 2022.Participants A total of 588 patients were included in the study.Interventions No interventions were administered.Primary and secondary outcome measures Knowledge, attitude and practice scores were measured using a self-administered questionnaire.Results Out of 588 patients included, 50.51% had undergone ASS. Lower education level and monthly income, shorter weekly exercise time and shorter disease duration were identified as independent risk factors for the KAP total score. Structural equation modelling revealed a direct positive effect of knowledge on attitude, but neither knowledge nor attitude influenced practice scores.Conclusions Patients with rotator cuff tears demonstrated relatively poor knowledge, a neutral attitude and moderate practice towards ASS, highlighting the need for patient education and counselling to enhance understanding and decision-making regarding ASS.

ObjectiveBacterial vaginosis is a disease caused by vaginal microecology disorder, which seriously affects female health. At present, there are many drugs to treat BV, and this study aims to compare the efficacy and safety of multiple drugs for BV through a network meta-analysis (NMA).MethodsAll studies were sourced from PubMed and Embase databases from the establishment date to April 13, 2023. We evaluated the clinical cure success rate and adverse effects (abnormal increase in vaginal discharge, external genital irritation, and vulvar itching) and performed subgroup analyses of the clinical cure success rate for different modes of administration. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis.ResultsWe included 42 studies that met the criteria, involving a total of 8382 patients. Network meta-analysis results showed that metronidazole and secnidazole had a higher rate of adverse reactions than placebo (RR 7.06; 95%-CI 2.61-19.10, RR 4.03; 95%-CI 1.63-9.98), the adverse reaction rate of probiotics group was lower than that of metronidazole group (RR 0.44; 95%-CI 0.21-0.93). The clinical cure rate of oral ornidazole was better than clindamycin (RR 16.08; 95%-CI 1.72-150.47), Secnidazole (RR 8.17; 95%-CI 1.66-40.25) and probiotics. Direct meta-analysis results showed that ornidazole had a better clinical cure rate than Secnidazole (RR 1.22; 95%-CI 1.10-1.34), oral ornidazole had a better clinical cure rate than Secnidazole (RR 1.23; 95%-CI 1.11-1.36). The clinical cure rate of vaginal application of sucrose was better than metronidazole (RR 1.12; 95%-CI 1.03-1.21) and metronidazole had a lower clinical cure rate than probiotics (RR 0.68; 95%-CI 0.52-0.88).ConclusionsThe results of this systematic review and network meta-analysis suggest that ornidazole may be an effective alternative for the treatment of BV, and that sucrose and probiotics are potential BV treatments that need to be validated by more high-quality clinical studies in the future.

PurposeThis retrospective study aimed to explore the efficiency and untoward reaction of liposomal paclitaxel versus docetaxel for locally advanced nasopharyngeal carcinoma (NPC).MethodsThis retrospective study included 115 patients diagnosed with NPC at our hospital between January 2018 and December 2021. Patients were stratified into two groups based on their treatment with either liposomal paclitaxel (n = 71) or docetaxel (n = 44) as part of the neoadjuvant chemotherapy regimen. Objective response rate (ORR), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were compared between the two groups.ResultsORR was significantly improved in the liposomal paclitaxel group than in the docetaxel group (62.0% versus 40.9%, p = 0.028). The 3-year PFS (PFS: 84.4% versus 77.5%, p = 0.303), LRFS (95.8% versus 94.4%, p = 0.810), DMFS (87.2% versus 83.0%, p = 0.443), and OS (90.7% versus 88.8%, p = 0.306) revealed no significance. The neutrophil-to-lymphocyte ratio [hazard ratio (HR): 3.510; p = 0.039] and distant metastasis (HR: 4.384; p = 0.035) were regarded as the risk factors using multivariate regression analysis. Moreover, the incidence of leukopenia at grades 1–2 in the liposomal paclitaxel group was significantly lower than that in the docetaxel group (28.1% versus 79.5%, p < 0.05).ConclusionsLiposomal paclitaxel had better efficacy in terms of short-term effects and lower incidence of leukopenia at grades 1–2 compared with the docetaxel group.

Ridge–furrow with plastic film mulching (RFPFM) is quite successful under dryland agriculture. However, its suitability for sunflower (Helianthus annuus L.) production with different plastic film mulching techniques such as ridge–furrow fully covered with plastic film mulching (FM) and half mulching (HM), in combination with appropriate nitrogen (N) fertilizer management remains uncertain. The current research investigated the performance of sunflower crop under three planting patterns (HM, FM and CP, i.e., conventional planting on flat land without plastic film mulching) and two N doses (120 and 240 kg N ha–1) in northwest China. The objectives were to evaluate the soil hydrothermal conditions, crop performance, water productivity (WP), N harvest index (NHI) and seed yield, under different combinations of these treatments. The results showed that both HM and FM had 1.8 °C higher topsoil temperature during seedling stage and soil moisture (+21 % and +30 %) during the whole growth stage, respectively, when compared to CP. The favorable hydrothermal conditions under HM and FM accelerated the seedling emergence and shortened the crop growth duration by nearly 5 days, and further improved seed yield (+23 and +33 %), WP (+26 and +36 %), and N uptake (+20 and +24 %), compared to CP. A comparison between FM and HM treatments did not show a significant increase in WP or yield for the former, despite improved soil hydrothermal conditions. In addition, increasing N application rate from 120 to 240 kg N ha–1 did not lead to a consistent and significant effect on total N uptake, WP and seed yield. Overall, the present study suggests that HM, when coupled with a reduced N dose, can replace FM in sunflower production. This approach reduces the use of plastic film and N fertilizer, while efficiently conserving water, enhancing WP and improving seed yield of sunflower under dry and semi–humid conditions.

Abstract Scene text in natural images carries additional semantic information to aid in image classification. Existing methods lack full consideration of the deep understanding of the text and the visual text relationship, which results in the difficult to judge the semantic accuracy and the relevance of the visual text. This paper proposes image classification based on Cross modal Knowledge Learning of Scene Text (CKLST) method. CKLST consists of three stages: cross‐modal scene text recognition, text semantic enhancement, and visual‐text feature alignment. In the first stage, multi‐attention is used to extract features layer by layer, and a self‐mask‐based iterative correction strategy is utilized to improve the scene text recognition accuracy. In the second stage, knowledge features are extracted using external knowledge and are fused with text features to enhance text semantic information. In the third stage, CKLST realizes visual‐text feature alignment across attention mechanisms with a similarity matrix, thus the correlation between images and text can be captured to improve the accuracy of the image classification tasks. On Con‐Text dataset, Crowd Activity dataset, Drink Bottle dataset, and Synth Text dataset, CKLST can perform significantly better than other baselines on fine‐grained image classification, with improvements of 3.54%, 5.37%, 3.28%, and 2.81% over the best baseline in mAP, respectively.

Abstract Background Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. Methods Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. Results The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five β-lactamase genes (bla GOB, bla BlaB, bla CME, bla OXA, and bla TEM) responsible for β-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that “metabolism” constituted the largest category within the core genome, while “information storage and processing” was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (β-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. Conclusion The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

Cobalt has emerged as a vital material in 10 nm technology for localized interconnect layers, potentially offering a compelling alternative to Cu-based interconnects. In this study, we subjected the contamination arising from the presence of cobalt atoms in silicon to comprehensive investigation, employing electron transmission electron microscopy (TEM) observations in conjunction with first-principles calculations. The results show that a dense CoSi layer with a thickness of a few nanometers is formed at the interface of cobalt and Si. The CoSi layer blocks the diffusion of Co atoms into Si. This is due to the semiconducting nature of the covalent bond formed between Co and Si, leading to the emergence of a forbidden zone at the Co/CoSi interface. The diffusion of Co into CoSi is governed by the atomic exchange mechanism, however, the local distortion of the periodic atomic potential due to the presence of the forbidden zone at the Co/CoSi interface hinders the diffusion of Co into Si. Therefore, the deposition of a Co metal layer on a Si chip does not require an additional barrier layer.

BackgroundClinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis.MethodsData of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups’ clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients’ prognosis.ResultsThere was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70–0.87; CSS: AUC 0.74–0.89).ConclusionAge, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.

To address the issue of partial feature loss in the single processing method within the time-frequency domain for roll grinding chatter, a combined time-frequency domain method is proposed to process signal feature. An intelligent algorithm is used to achieve online prediction of roll grinding chatter. Firstly, the empirical mode decomposition (EMD) method is utilized to decompose the vibration sensor signals, extrating the intrinsic mode function (IMF) while removing "spurious components" to calculate time domain characteristics associated with roll grinding chatter. Then, wavelet packet energy entropy is used to solve the frequency band node energy entropy values of acoustic emission sensor signals, obtaining frequency domain features characterizing the roll grinding chatter. Finally, the time-frequency domain features after dimension reduction is substituted into the intelligent algorithm model for online prediction of the roller grinding process. The results show that the the LV-SVM model achieves an average classification accuracy of 92.75%, with an average response time of 0.776 5 s. This verifies the validity of EMD and LV-SVM based on wavelet packet energy entropy in the time-frequency domain for online prediction of roller grinding chatter.

Abstract Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.

Digitalization represents a pivotal global development trend and serves as a significant force propelling economic and social transformation. This manuscript uses the global Malmquist–Luenberger (GML) model to estimate green total factor productivity (GTFP) across 284 Chinese cities from 2003 to 2018, taking the pilot policy of “construction and application of e-government public platforms based on cloud computing” as an example to assess the impact of government digital transformation on the qualitative development of the economy by using a difference-in-differences model to explore the path of its role and driving mechanism. The results reveal that government digital transformation promotes the qualitative improvement of the city’s economic development, and its driving effect shows a marginal incremental law. Moreover, government digital transformation can contribute to the formation of a “latecomer advantage” in the lagging regions, which creates a “catch-up effect” on the regions with favorable development foundations, excellent geographical conditions, high urban ranking, and high education quality. Additionally, government digital transformation boosts economic and social development quality through both innovation spillover and structural optimization.

BackgroundInsomnia affects the quality of life of a significant number of individuals worldwide. Despite the fact that pharmaceutical sleep treatments have shown brief enhancements in sleep quality, these are still not recommended for the long-term management of sleep issues. To deal with this problem, our study aims to assess the effectiveness of auricular acupressure for treating insomnia by conducting a systematic review and meta-analysis.MethodData from randomized controlled trials (RCTs) of auricular acupressure for insomnia was collected from five English-language databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, and CINAHL) and four Chinese databases (CBM, CNKI, CQVIP, and Wanfang). Relevant data were extracted by two reviewers. I2 statistics were adopted to appraise heterogeneity. A network meta-analysis was applied to compare the effect of auricular acupressure with other methods.ResultIn all, 23 RCTs involving a total of 1,689 patients were included. The results demonstrated a significant decrease in the Pittsburgh Sleep Quality Index (PSQI) score for the intervention group compared to the control group [SMD = −1.30, 95% CI (−1.65, −0.96), I2 = 90%]. Furthermore, the group receiving auricular acupressure in addition to usual care showed a lower PSQI score compared to the usual care group [SMD = −1.13, 95% CI (−1.33, −0.93), I2 = 23%]. Auricular acupressure was found to enhance the effectiveness of estazolam in improving PSQI score, with the combination of auricular acupressure and estazolam resulting in a lower PSQI score [MD = −4.8, 95% CI (−7.4, −2.1)]. Importantly, no serious adverse events were reported. In patients with insomnia following stroke, the intervention group (which received auricular acupressure) exhibited a lower PSQI score compared to the control group [SMD = −0.74, 95% CI (−1.03, −0.46), I2 = 0%]. Similarly, in patients with insomnia related to cancer, the intervention group (receiving auricular acupressure) demonstrated a lower PSQI score compared to the control group [SMD = −0.99, 95% CI (−1.37, −0.61), I2 = 0%].ConclusionThe effects of auricular acupressure on insomnia are comparable to those of estazolam. Furthermore, auricular acupressure can serve as a complementary treatment to estazolam or other interventions, effectively improving symptoms of insomnia.

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

To solve the problem of bolt defects in unmanned aerial vehicle inspection that are difficult to identify quickly and accurately, this paper proposes a defect detection method based on the improved YOLOv5 anchor mechanism. Firstly, the Normalized Wasserstein distance (NWD) evaluation metric and the Intersection over Union evaluation metric are combined, and the experiment determines the appropriate weight for this combination. This way, the sensitivity of using IoU alone to small objecet detection anchor box threshold changes was reduced. Furthermore, Convolutional Block Attention Module is included into the head network architecture of yolov5 in order to prioritize significant information and suppress irrelevant features. Omni-dimensional Dynamic Convolution (ODConv) is used to replace convolution in MobileNetv2. The combination module is used as the new backbone of the YOLOv5 model. It simultaneously enhances the model’s capability to extract bolt defect object information, minimizes calculation requirements, and achieves lightweight detection across the entire model. Compared with the original algorithm, the model detection Accuracy Precision (AP) is increased by 30.1%, the mean Accuracy Precision is increased by 30.4%. Other evaluation metrics of the model, such as GFlOPs and Parameters, all decreased slightly. The above results show that the improved algorithm proposed in this paper greatly improves the detection accuracy of the model on the premise of ensuring that the model is as small as possible.

Objective: Anti-inflammatory and anti-apoptotic therapy is expected to become the focus for attenuating cerebral ischemia‒reperfusion injury (CIRI), but the underlying mechanism needs to be further elucidated. Zc3h12d has been reported to downregulate NF-κB signaling pathway. Nevertheless, no studies have been conducted to investigate whether Zc3h12d is associated with the development of CIRI. The aim of this study was to investigate whether Zc3h12d can ameliorate CIRI and the underlying mechanism. Methods: MCAO/R and OGD/R were performed to mimic CIRI in vitro and in vivo, respectively. The expression levels of Zc3h12d, proinflammatory cytokines, proapoptotic protein, and p-p65 were detected by RT‒qPCR, ELISA or Western blotting assays. Immunofluorescence staining was used to detect the spatial distribution of Zc3h12d and the expression of p-p65 in the nucleus. Apoptotic analyses were performed by TUNEL staining, Nissl staining and flow cytometry. Cell viability was assessed using the CCK-8 assay. Results: CIRI increased Zc3h12d expression and neuronal apoptosis in the brain. Zc3h12d was predominantly located in neurons in the cortex. Overexpression of Zc3h12d can inhibit inflammation and suppress neuronal apoptosis in cells after CIRI. Furthermore, overexpression of Zc3h12d decreased the expression of p-p65 in the nucleus, which was attenuated by TNF-α, a common NF-κB agonist. In addition, overexpression of Zc3h12d can also shorten the half-life of proinflammatory cytokines. Conclusion: Zc3h12d may play a crucial role in inhibiting inflammation and apoptosis after CIRI, and the underlying mechanism may be related to repressing the activation of NF-κB signaling. Targeting Zc3h12d may be a novel strategy for preventing CIRI.

Abstract Purpose We aimed to investigate the efficacy and side effects of concurrent chemoradiotherapy, with or without nimotuzumab, for the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy. Methods This study retrospectively enrolled 109 patients with NPC from our hospital from July 2019 to May 2021.All patients were treated with docetaxel, cisplatin, and fluorouracil(TPF) neoadjuvant chemotherapy for 2 cycles, and concurrent chemoradiotherapy was performed 2 weeks after chemotherapy. According to whether nimotuzumab was added in concurrent chemoradiotherapy, they were divided into the nimotuzumab group and the control group, with 52 cases in the nimotuzumab group and 57 cases in the control group.The efficacy and adverse reactions of the two groups were retrospectively analyzed. Results The objective remission and complete remission rates in the nimotuzumab and control groups were 100% vs 98.2% (p = 1.000), and 92.3% vs 78.9% (p = 0.049), respectively. The 3-year distant metastasis-free survival of the nimotuzumab and control groups was 91.6% and 77.3% (p = 0.047), respectively.The 3-year progression-free survival, locoregional relapse-free survival, and overall survival of the nimotuzumab and control groups were 87.6% vs 75.5% (p = 0.110), 90.5% vs 86.9% (p = 0.566), and 94.5% vs 87.1% (p = 0.295), respectively. In the nimotuzumab group, subgroup analysis showed that patients aged 0.05). Conclusion The concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma achieved a higher complete remission rate and significantly improved distant metastasis-free survival compared with concurrent chemoradiotherapy alone. Additionally, an increasing trend was observed in progression-free survival, and the incidence of side effects was similar in both groups.

To determine the effects of C/A ratio (CaO/Al2O3) and the basicity B (CaO/SiO2) of Al2O3–CaO–SiO2–MgO(–CaF2) refining slags on the characteristics of inclusions and sulfur (S) content in 316L stainless steels, equilibrium experiments between the slag and steel were carried out at 1873 K under laboratory conditions. Thermodynamic investigations were performed to understand how the chemical compositions of the inclusions changed and to evaluate the desulfurization capabilities of the refining slags. Additionally, a mathematical model was established for predicting the separation of nonmetallic inclusions during refining and characterizing the movements of the inclusions at the “slag–steel” interface. First, the findings showed that increasing the slag basicity B in the range of 1.0–7.0 led to a reduction in the dissolved [O] mass fraction from 0.0033% to 0.0021% and the total oxygen (T.O.) from 0.0050% to 0.0031% while also slightly improving the cleanliness of the steel by increasing the C/A ratio within the range 1.0–2.2. Then, the average compositions of the inclusions in the steel were approximately (mol pct SiO2)/(mol pct MnO) = 0.57 (±0.08), and the Al2O3 content grew from 6.55% to 18.36% (mol pct), while increasing the slag basicity B resulted in an increase in the Al2O3 content of the inclusions. Once the B exceeded 5.0, further increases in the slag basicity did not continuously increase the desulfurization capability. Finally, all calculations of refining slag with the model yielded separation rates were higher than 80% for inclusions with diameters of 5 μm. For inclusion removal after slag refining, the results of the experiments exhibited consistent agreement with the predictions from the mathematical model.

With the rapid increase of penetration level of new energy power generation, the construction of auxiliary service market is facing new challenges. The stricter requirements of the power plant unit AGC are proposed by the power system. How to coordinate and control the output of hydropower and thermal power units to increase the use of hydropower while meeting the requirements of AGC regulation is a problem to be solved. Under the condition of interconnection of units in the whole network, an optimal control strategy for joint commissioning of hydropower and thermal power plants that meets the performance conditions of ‘two rules’ is proposed in this paper. The strategy establishes the connection between hydropower and thermal power units. Combined with the output characteristics and economic characteristics of hydropower units and thermal power units, a coordinated optimization control strategy model of hydropower and thermal power AGC units suitable for the ’two rules’ assessment rules is proposed for each objective and constraint condition in the joint scheduling of hydropower and thermal power. The optimal mathematical model with multiple objectives is constructed to realize the distribution of AGC among different types of power plants and units, which can give full play to the regulation ability of hydropower and thermal power. The proposed strategy achieves the efficient use of clean energy and reduces the grid’s overall operating costs to achieve energy conservation and emission reduction. Simulation results verify the superiority of the proposed strategy.

This paper presents a method to analyze the Sub Synchronous Oscillation (SSO) problem based on broad learning system (BLS), which can quickly analyze the risk of SSO in a system and take measures. The simulation system is constructed by the eigenvalue analysis method to obtain training data, that solves the problem which is difficult to obtain actual data in SSO problem and makes the model more accurate and the conclusion more convincing. Subsequently, BLS is applied for feature extraction and the prediction model is constructed, the model can show the deep relationship between the oscillation source and topology of the system as well as various operating data, which is difficult to be expressed by formula. The system was tested and validated in the 41-bus system. The feature importance analysis method which comes from eXtreme Gradient Boosting (XGboost) algorithm is proposed and combined with the BLS prediction model, which can analyze the influence of each variable on the prediction results in different series compensation levels, and is validated in the 41-bus system, that makes the results of prediction more interpretable. Finally, the results of simulation show that the model can predict data with high accuracy and give adjustment plans for effective control of the system to avoid the risk of SSO.

The grains, cellular structures, dislocation densities, and oxides in L-PBF 316LSS were systematically characterized. The microstructure evolution and mechanical properties were closely associated with the scanning speed. The sizes of grains and oxides in L-PBF 316LSS significantly decreased with increasing scanning speed, while the dislocation density remained relatively stable for speeds from 500 to 900 mm s−1 and significantly increased when the scanning speed exceeded 900 mm s−1. The tensile samples exhibited obvious anisotropic mechanical properties, and the TD samples showed higher strength, attributed to the strong crystallographic orientation, while -oriented grains facilitated activation and generation of deformation twins. Importantly, the cellular substructures were traversed by deformation twins, leading to their subdivision and dissociation. The discontinuous dislocation tangles interacted with deformation twins and provided a continuous and stable work hardening capability, resulting in superior ductility of BD samples. Reasonable agreement between the yield strength experimental results and theoretical calculations was achieved, suggesting that the superior strength and ductility for L-PBF 316LSS can be attributed to the grain boundary strengthening, oxide dispersion strengthening, dislocation strengthening and work hardening behavior. Collectively, this study revealed the strengthening mechanism of L-PBF 316 L stainless steel, which can provide theoretical guidance in the development of new alloy materials.

This review was undertaken to summarize the development, experience, and challenges of ratoon rice cultivation over 50 years in Jiangxi Province, China. As the growing labor shortage in the last decade, rice ratooning technology with the main crop harvested mechanically has widely spread and quickly replaced the traditional ratoon rice under manual harvesting. However, rolling damage caused by harvesting machines becomes a critical factor for yield loss in the ratoon season. Some key agronomic practices including variety selection, optimal planting time, nutrient and water management, etc. were discussed here for minimizing rolling damage and achieving high grain yield in the ratoon crop under mechanical harvesting. Besides, some innovative crop rotation systems have been attempted by integrating ratoon rice with duck farming or fragrant taro for reducing weeds and disease incidences and improving farmers' profit. At last, this review analyzed the challenges and opportunities for further expansion of ratoon rice production in Jiangxi from the perspective of cultivation technology, rice market, and government policy.

Abstract Small object detection remains a bottleneck because there is little visual information about them, especially in the deep layers. To improve the detection performance of small objects, here, Swin Transformer is introduced as the model backbone network to extract rich features of small objects. Then, a multilevel receptive field expansion network (MRFENet) is proposed based on the characteristics of different stages in the Swin Transformer. Specifically, a receptive field expansion block (RFEB) is designed to acquire contextual cues and extract detailed information. The RFEB is carefully designed to target the required receptive fields of different layers and further refine the features. MRFENet combined with RFEBs implements the retention of small object context cues and the acquisition of receptive fields for the adaptive detection tasks. Finally, a union loss function is designed to enhance the localization ability. Experiments on the MS COCO dataset demonstrate that the proposed MRFENet has a significant improvement against other state‐of‐the‐art methods, which further validates that MRFENet can effectively utilize small object information.

Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues, the extensive clinical application of PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis. The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy (MWDT) tested on HCT15 colorectal cancer (CRC) cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20 μg/mL. The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor. Furthermore, Cu-Cy mediated MWDT could deplete glutathione peroxide 4 (GPX4) and enhance lipid peroxides (LPO) and malondialdehyde (MDA). Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis. The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model. Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy + MW group was significantly lower than that in other groups. Overall, these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis, which provides a potential solution for cancer resistance.

Summary: Circular RNAs (circRNAs) are crucial regulators of β-cell function and are involved in lipotoxicity-induced β-cell damage in type 2 diabetes mellitus (T2DM). We previously identified that circGlis3, a circRNA derived from exon 4 of the diabetes susceptibility gene Glis3, was upregulated in lipotoxic β cells. However, the functional role and molecular mechanism of circGlis3 in β cells remain largely unknown. Here, we revealed that the splicing factor CUGBP Elav-Like Family Member 1 (CELF1) facilitated the biogenesis of circGlis3. Moreover, we established a transgenic mouse model and confirmed that the overexpression of circGlis3 impaired β-cell function. Mechanistically, circGlis3 bound to heterogeneous nuclear ribonucleoprotein F (hnRNPF) and blocked its nuclear translocation, thereby reducing Sirt1 levels. Additionally, circGlis3 encoded a 348aa protein that interacted with GLIS3 and inhibited its transcriptional activity. Our data uncover a critical role of circGlis3 in β-cell dysfunction, suggesting that circGlis3 may be a potential therapeutic target for T2DM.

Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural product with multiple biological functionsand. Recent investigations have illuminated PTN's protective properties against neurological maladies; however, its potential therapeutic role against AD remains uncharted. This study aims to explore the role of PTN in treating AD. Our in vitro findings underscore PTN's bioactivity, as evidenced by its capacity to curtail apoptosis, reduce reactive oxygen species (ROS) production, and restore mitochondrial membrane potential in PC12 cells. Moreover, PTN treatment demonstrates a capacity to ameliorate deficits in spatial learning and memory in the 3 ×Tg-AD murine model. Notably, PTN's therapeutic efficacy surpasses that of a clinical agent, donepezil. Mechanistically, PTN's neuroprotective effects stem from its adept regulation of the AMPK/GSK3β(ser9)/Nrf2 signaling pathway and protection on neuronal cells from ROS-related apoptosis. Although the molecular target and the pre-clinical evaluations of PTN need to be further explored, this study indicates PTN as a potential agent or lead compound for the drug development against AD.

AbstractObjective To evaluate the therapeutic effect of high-intensity focused ultrasound (HIFU) treatment for adenomyotic patients with primary infertility and to explore the factors that affect the pregnancy outcomes.Materials and methods Twenty-seven adenomyotic patients with primary infertility who underwent HIFU at HUNAN Provincial Maternal and Child Health Care Hospital, China, between July 2018 and December 2022 were retrospectively reviewed. We evaluated the pregnancy outcomes and analyzed the factors that may affect pregnancy outcomes including time to conception, pregnancy approach, gestational age, delivery mode, neonatal outcomes, and complications during pregnancy and delivery.Results Among the 27 adenomyotic patients with primary infertility, 10 patients had a total of 11 pregnancies after HIFU treatment. Of these, eight (72%) cases were natural pregnancies and three (23%) were in vitro fertilization (IVF) pregnancies. The median time to conception was 10 (range 4–25) months. There were eight (72%) successful deliveries. The rate of full-term deliveries was 90%. Of the eight live births, four (50%) were born vaginally and four (50%) by cesarean section. No severe complications occurred. The mean birth weight of newborns was 3.1 (range: 2.3–3.9) kg; all newborns developed well without complications during postpartum and breastfeeding.Conclusions HIFU treatment for adenomyosis could improve fertility of patients with primary infertility. HIFU is a promising therapeutic approach for patients with adenomyosis and infertility who wish to achieve pregnancy and have live birth deliveries.

AbstractObjective To compare the efficacy and safety of different treatment options for cervical pregnancy (CP).Materials and methods A total of 74 patients diagnosed with CP at Hunan Provincial Maternal and Child Health Care Hospital between January 2016 and September 2022 were retrospectively analyzed. Among them, 31 were treated with uterine artery embolization (UAE) followed by hysteroscopic curettage, 34 were treated with hysteroscopic curettage alone, and nine were treated with high-intensity focused ultrasound (HIFU) followed by hysteroscopic curettage. Medical records and pregnancy outcomes were analyzed.Results There were no significant differences in age, gravidity, parity, abortion, or preoperative hemoglobin levels among the patients in the three groups; however, significant differences in gestational age, gestational sac diameter, preoperative β-hCG, and presence of cardiac pulsation were observed (p

Abstract Background Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive. Methods Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC–MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. Results A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC. Conclusions circINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.

To address the undesirable reactions associated with matrine (MAT) injection in clinical settings, a high-loading drug delivery system (DDS) based on pH-sensitive molecularly imprinted polymer (MAT@MIPs) was prepared for the first time. The imprinted materials containing recognition sites for the matrine were formed by using carboxyl-functionalized multiwalled carbon nanotubes as a supportive matrix and dopamine as a cross-linker due to its exceptional biocompatibility. Subsequently, the optimal reaction conditions and adsorption performance of MAT@MIPs were systematically investigated. The obtained polymers were characterized and evaluated by Fourier transform infrared spectrometry, scanning electron microscopy, elemental analysis, and thermogravimetric analysis. Results indicated that the MIPs demonstrated a favorable imprinting factor (2.36) and a high binding capacity (21.48 mg·g−1) for matrine. In vitro studies, we performed cell counting kit-8 assays in HepG2 cells, then the drug delivery capabilities of MAT-loaded MIPs were validated through light microscopy analyses, and the matrine content in culture medium was quantified using ultra high-performance liquid chromatography-mass spectrum synchronously. The facile fabrication of MAT@MIPs presents a viable solution for designing high-loading and pH-responsive DDS, which can offer a novel administration approach for drugs requiring injection in clinical applications.

Lockdowns and border closures due to COVID-19 imposed mental, social, and financial hardships in many societies. Living with the virus and resuming normal life are increasingly being advocated due to decreasing virus severity and widespread vaccine coverage. However, current trends indicate a continued absence of effective contingency plans to stop the next more virulent variant of the pandemic. The COVID-19–related mask waste crisis has also caused serious environmental problems and virus spreads. It is timely and important to consider how to precisely implement surveillance for the dynamic clearance of COVID-19 and how to efficiently manage discarded masks to minimize disease transmission and environmental hazards. In this viewpoint, we sought to address this issue by proposing an appropriate strategy for intelligent surveillance of infected cases and centralized management of mask waste. Such an intelligent strategy against COVID-19, consisting of wearable mask sample collectors (masklect) and voiceprints and based on the STRONG (Spatiotemporal Reporting Over Network and GPS) strategy, could enable the resumption of social activities and economic recovery and ensure a safe public health environment sustainably.

To investigate the stabilization mechanism of microbial necromass carbon (C) in rice paddy soil, the accumulation of microbial necromass and its contribution to SOC in bulk soil and in various fractions were addressed under a 40-year fertilization trial. The fertilization regimes included no fertilizer (Control), nitrogen, phosphorus and potassium inorganic fertilizer (NPK), and inorganic fertilizer plus manure (NPKM). Coarse particulate organic matter (cPOM), fine inter-microaggregate POM (fPOM), intra-microaggregate POM (iPOM), non-occluded silt plus clay fraction (s + c_f), and silt plus clay occluded within microaggregates (s + c_m) fractions were isolated. The results indicated that fungal necromass were the main component of microbial necromass across the fractions; however, the bacterial role was enhanced in mineral fractions (s + c_f and s + c_m) compared to POM fractions (cPOM, fPOM, and iPOM). The iPOM and mineral fractions stored more than 90 % of microbial necromass C due to the physical protection (organo-mineral associations and occlusion within microaggregates). Compared to Control, the significantly increased content of microbial necromass C and its contribution to SOC in bulk soil were attributed to the enhanced content of fungal necromass in iPOM fraction under NPK treatment. The highest content of microbial necromass C was found under NPKM treatment; moreover, the increased content of microbial necromass C in iPOM and s + c_m fractions made up to 82.80 % of that in bulk soil compared to Control, while a saturation behavior was found in s + c_f fraction. The contribution of microbial necromass to SOC was not altered under NPKM treatment compared to Control. However, a reduced fungal/bacterial necromass C ratio was found in bulk soil and iPOM fraction under NPKM treatment compared to Control, mainly due to the supply of higher quality substrates and the increased soil pH. As a whole, this study revealed the diverse responses of microbial necromass C accumulation and its contribution to SOC under different fertilization regimes in paddy soil.

Abstract Background Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal cancers worldwide accompany with an extremely poor prognosis. Therefore, this study aims to screen for new molecules affecting ESCC and explore their mechanisms of action to provide ideas for targeted therapies for ESCC. Methods Firstly, we screened out the membrane protein SCARA5 by high-throughput sequencing of the ESCC patient tissues, and RT-qPCR and WB were used to verify the differential expression of SCARA5 in esophageal cell lines, and IHC analyzed the expression localization of SCARA5 in ESCC tissue. Then, flow cytometry, wound healing assay, Transwell assay and CCK-8 assay were used to explore the effects of SCARA5 on cell cycle, migration and invasion as well as cell proliferation activity of esophageal squamous carcinoma cells. Meanwhile, transmission electron microscopy was used to detect changes in cellular mitochondrial morphology, and flow cytometry were used to detect changes in intracellular reactive oxygen metabolism, and immunofluorescence and flow cytometry were used to detect changes in intracellular Fe2+. Mechanistically, co-immunoprecipitation was used to detect whether SCARA5 binds to ferritin light chain, and ferroptosis-related protein expression was detected by WB. Finally, the tumor xenograft model was applied to validation the role of SCARA5 tumor growth inhibition in vivo. Results We found that SCARA5 was aberrantly decreased in ESCC tissues and cell lines. Furthermore, we confirmed that SCARA5 suppressed the cell cycle, metastasis and invasion of ESCC cells. Meanwhile, we also found that overexpression of SCARA5 caused changes in mitochondrial morphology, accumulation of intracellular reactive oxygen species and increased intracellular Fe2+ in ESCC cells, which induced ferroptosis in ESCC cells. Mechanically, we validated that SCARA5 combined with ferritin light chain and increased intracellular Fe2+. As well as, overexpression SCARA5 induced ferroptosis by increasing ferritin light chain in nude mice subcutaneous tumors and inhibited the growth of nude mice subcutaneous tumors. Conclusion Collectively, our findings demonstrated that SCARA5 suppressed the proliferation and metastasis of ESCC by triggering ferroptosis through combining with ferritin light chain.

Based on the obtained SARs, further structural optimisation of compound BC2021-104511-15i was conducted in this investigation, and totally ten novel quinoline derivates were designed, synthesised and optimised for biological activity. Among them, compound 10a displayed significant in vitro anticancer activity against COLO 205 cells with an IC50 value of 0.11 μM which was over 90-fold more potent than that of Regorafenib (IC50>10.0 μM) and Fruquintinib (IC50>10.0 μM). Furthermore, compound 10a exhibited over 90-fold selectivity towards COLO 205 relative to human normal colorectal mucosa epithelial cell FHC cells. Flow cytometry study demonstrated that compound 10a could induce apoptosis in COLO 205 cells, however, it could not induce cell cycle arrest in COLO 205 cells. The results of preliminary kinase profile study showed that compound 10a was a potential HGFR and MST1R dual inhibitor, with IC50 values of 0.11 μM and 0.045 μM, respectively.

BackgroundThe accurate etiology of mitral valve aneurysm (MVA) formation is not completely understood, and the most effective management approach for this condition remains controversial.MethodsWe retrospectively analyzed 20 MVA patients who underwent either surgical interventions or conservative follow-ups at the Zhongnan Hospital of Wuhan University between 2017 and 2021. We examined their clinical, echocardiographic, and surgical records and tracked their long-term outcomes.ResultsOf the 20 patients, 12 were diagnosed with MVA using transthoracic echocardiography, seven required additional transesophageal echocardiography for a more definitive diagnosis, and one child was diagnosed during surgery. In all these patients, the MVAs were detected in the anterior mitral leaflet. We found that 15 patients (75%) were associated with infective endocarditis (IE), whereas the remaining patients were associated with bicuspid aortic valve and moderate aortic regurgitation (AR) and mild aortic stenosis (5%), congenital heart disease (5%), elderly calcified valvular disease (5%), mitral valve prolapse (5%), and unknown reasons (5%). Of the 17 patients who underwent hospital surgical interventions, two died due to severe cardiac events. The remaining 15 patients had successful surgeries and were followed up for an average of 13.0 ± 1.8 months. We observed an improvement in their New York Heart Association functional class and mitral regurgitation and AR degrees (P-value

ObjectiveThe gut micro-biome plays a pivotal role in the progression of lung cancer. However, the specific mechanisms by which the intestinal microbiota and its metabolites are involved in the lung cancer process remain unclear.MethodStool samples from 52 patients with lung cancer and 29 healthy control individuals were collected and subjected to 16S rRNA gene amplification sequencing and non-targeted gas/liquid chromatography-mass spectrometry metabolomics analysis. Then microbiota, metabolites and potential signaling pathways that may play an important role in the disease were filtered.ResultsFirmicutes, Clostridia, Bacteroidacea, Bacteroides, and Lachnospira showed a greater abundance in healthy controls. In contrast, the Ruminococcus gnavus(R.gnavus) was significantly upregulated in lung cancer patients. In this respect, the micro-biome of the squamous cell carcinoma(SCC)group demonstrated a relatively higher abundance of Proteobacteria, Gammaproteobacteria, Bacteroides,and Enterobacteriaceae, as well as higher abundances of Fusicatenibacter and Roseburia in adenocarcinoma(ADC) group. Metabolomic analysis showed significant alterations in fecal metabolites including including quinic acid, 3-hydroxybenzoic acid,1-methylhydantoin,3,4-dihydroxydrocinnamic acid and 3,4-dihydroxybenzeneacetic acid were significantly altered in lung cancer patients. Additionally, the R.gnavus and Fusicatenibacter of lung cancer were associated with multiple metabolite levels.ConclusionOur study provides essential guidance for a fundamental systematic and multilevel assessment of the contribution of gut micro-biome and their metabolites in lung cancer,which has great potential for understanding the pathogenesis of lung cancer and for better early prevention and targeted interventions.

BackgroundPancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive cancer that has been reported primarily as case reports. Due to limited large-scale epidemiological and prognostic analyses, the outcomes of PSRCC patients varies greatly in the absence of recognized first-line treatment strategies. This study aimed to compare the clinical features, treatment, and prognosis of PSRCC and pancreatic ductal cell carcinoma (PDAC), the most common subtype of pancreatic cancer, and to establish predictive models for these subtypes.MethodsThe data on PSRCC and PDAC patients from 1998 to 2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Thereafter, the clinical, demographic, and treatment characteristics of the two groups and the differences and influencing factors of the two groups were evaluated by propensity score matching (PSM), Kaplan–Meier survival curves, Cox risk regression analyses, and least absolute shrinkage and selection operator (LASSO) analysis. Next, prognosis models were constructed and validated by KM and ROC analysis. Finally, a nomogram was constructed, based on the results of these analyses, to predict survival outcomes of PSRCC and PDAC patients.ResultsA total of 84,789 patients (432 PSRCC and 84357 PDAC patients) were included in this study. The results of the study revealed that, compared to the PDAC patients, PSRCC patients were more likely to be male, aged between 58–72 years, have larger tumor masses, and less likely to undergo chemotherapy. Before PSM, the overall survival and cancer-specific survival of the PSRCC group were significantly lower than those PDAC group, but there was no difference in the prognosis of the two groups after PSM. Additionally, lymph node ratio (LNR), log odds of positive lymph node (LODDS), tumor size, age, T-stage, marital status, and summary stage were found to be independent prognostic factors for PSRCC. Lastly, the prediction model and nomogram based on these prognostic factors could accurately predict the survival rate of the patients in SEER datasets and external validation datasets.ConclusionThe prognosis of PSRCC and PDAC patients is similar under the same conditions; however, PSRCC patients may have more difficulty in receiving better treatment, thus resulting in their poor prognosis.

Ischemic-reperfusion injury (IRI) is a major pathogenic factor in acute kidney injury (AKI), which directly leads to the hypoxic injury of renal tubular epithelial cells (RTECs). Although emerging studies suggest repressor element 1–silencing transcription factor (REST) as a master regulator of gene repression under hypoxia, its role in AKI remains elusive. Here, we found that REST was upregulated in AKI patients, mice, and RTECs, which was positively associated with the degree of kidney injury, while renal tubule–specific knockout of Rest significantly alleviated AKI and its progression to chronic kidney disease (CKD). Subsequent mechanistic studies indicated that suppression of ferroptosis was responsible for REST-knockdown-induced amelioration of hypoxia-reoxygenation injury, during which process Cre-expressing adenovirus–mediated REST downregulation attenuated ferroptosis through upregulating glutamate-cysteine ligase modifier subunit (GCLM) in primary RTECs. Further, REST transcriptionally repressed GCLM expression via directly binding to its promoter region. In conclusion, our findings revealed the involvement of REST, a hypoxia regulatory factor, in AKI-to-CKD transition and identified the ferroptosis-inducing effect of REST, which may serve as a promising therapeutic target for ameliorating AKI and its progression to CKD.

Efficient ground operation of aircraft directly impacts airport's courses of energy conservation and green operation. Typical runway configurations used in large airport were classified and analyzed. Combining with flight ground operation, 2 methods of comparison and selection of carbon emission were proposed, which were based on taxiing distance and simulation respectively. In addition, above 2 methods were applied in large-sized airport runways configuration selection and taxiways optimization. Application results show that the method based on taxiing distance suits for rough estimation in the early stage of airport planning, the method based on simulation considering both ground taxiing and delay time suits for a more detailed study on airport planning.

Abstract Background Acinetobacter baumannii has emerged as the major opportunistic pathogen in healthcare-associated infections with high-level antibiotic resistance and high mortality. Quorum sensing (QS) system is a cell-to-cell bacterial communication mediated by the synthesis, secretion, and binding of auto-inducer signals. It is a global regulatory system to coordinate the behavior of individual bacteria in a population. The present study focused on the QS system, aiming to investigate the regulatory role of QS in bacterial virulence and antibiotic resistance. Method The auto-inducer synthase gene abaI was deleted using the A. baumannii ATCC 19606 strain to interrupt the QS process. The RNA-seq was performed to identify the differentially expressed genes (DEGs) and pathways in the mutant (△abaI) strain compared with the wild-type (WT) strain. Results A total of 380 DEGs [the adjusted P value log21.5] were identified, including 256 upregulated genes and 124 downregulated genes in the △abaI strain. The enrichment analysis indicated that the DEGs involved in arginine biosynthesis, purine metabolism, biofilm formation, and type VI secretion system (T6SS) were downregulated, while the DEGs involved in pathways related to fatty acid metabolism and amino acid metabolism were upregulated. Consistent with the expression change of the DEGs, a decrease in biofilm formation was observed in the △abaI strain compared with the WT strain. On the contrary, no obvious changes were found in antimicrobial resistance following the deletion of abaI. Conclusions The present study demonstrated the transcriptomic profile of A. baumannii after the deletion of abaI, revealing an important regulatory role of the QS system in bacterial virulence. The deletion of abaI suppressed the biofilm formation in A. baumannii ATCC 19606, leading to decreased pathogenicity. Further studies on the role of abaR, encoding the receptor of auto-inducer in the QS circuit, are required for a better understanding of the regulation of bacterial virulence and pathogenicity in the QS network.

Abstract Background Impairments in upper limb motor function and cognitive ability are major health problems experienced by stroke patients, necessitating the development of novel and effective treatment options in stroke care. The aim of this study is to examine the effects of robot-assisted therapy on improving upper limb and cognitive functions in stroke patients. Methods This will be a single-blinded, 2-arm, parallel design, randomized controlled trial which will include a sample size of 86 acute and subacute stroke patients to be recruited from a single clinical hospital in Shanghai, China. Upon qualifying the study eligibility, participants will be randomly assigned to receive either robot-assisted therapy or conventional therapy with both interventions being conducted over a 6-week period in a clinical rehabilitation setting. In addition to comprehensive rehabilitation, the robot-assisted therapy group will receive a 30-min Armguider robot-assisted therapy intervention 5 days a week. Primary efficacy outcomes will include Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Mini-Mental Status Examination (MMSE). Other secondary outcomes will include Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Rey–Osterrieth Complex Figure Test (ROCFT). All trial outcomes will be assessed at baseline and at 6-week follow-up. Intention-to-treat analyses will be performed to examine changes from baseline in the outcomes. Adverse events will be monitored throughout the trial period. Discussion This will be the first randomized controlled trial aimed at examining the effects of robot-assisted therapy on upper limb and cognitive functions in acute and subacute stroke patients. Findings from the study will contribute to our understanding of using a novel robotic rehabilitation approach to stroke care and rehabilitation. Trial registration Chinese Clinical Trial Registry ChiCTR2100050856 . Registered on 5 September 2021.

Organoids are stem cell-derived, self-organizing, 3D structures. Compared to the conventional 2D cell culture method, 3D cultured organoids contain a variety of cell types that can form functional “micro-organs” and can be used to simulate the occurrence process and physiological pathological state of organ tissues more effectively. Nanomaterials (NMs) are becoming indispensable in the development of novel organoids. Understanding the application of nanomaterials in organoid construction can, therefore, provide researchers with ideas for the development of novel organoids. Here, we discuss the application status of NMs in various organoid culture systems and the research direction of NMs combined with organoids in the biomedical field.

Gastric cancer (GC), a common and high-mortality disease, still occupies an important position in current cancer research, and Helicobacter pylori (H. pylori) infection as its important risk factor has been a hot and challenging research area. Among the numerous pathogenic factors of H. pylori, the virulence protein CagA has been widely studied as the only bacterial-derived oncoprotein. It was found that CagA entering into gastric epithelial cells (GECs) can induce the dysregulation of multiple cellular pathways such as MAPK signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, Wnt/β-catenin signaling pathway, JAK-STAT signaling pathway, Hippo signaling pathway through phosphorylation and non-phosphorylation. These disordered pathways cause pathological changes in morphology, adhesion, polarity, proliferation, movement, and other processes of GECs, which eventually promotes the occurrence of GC. With the deepening of H. pylori-related research, the research on CagA-induced abnormal signaling pathway has been updated and deepened to some extent, so the key signaling pathways activated by CagA are used as the main stem to sort out the pathogenesis of CagA in this paper, aiming to provide new strategies for the H. pylori infection and treatment of GC in the future.

Longitudinal optical field modulation is of critical importance in a wide range of applications, including optical imaging, spectroscopy, and optical manipulation. However, it remains a considerable challenge to realize a uniformly distributed light field with extended depth-of-focus. Here, a high-efficiency extended depth-of-focus metalens is proposed by adjoint-based topology-shape optimization approach, wherein the theoretical electric field intensity corresponding to a variable focal-length phase is utilized as the figure of merit. Using a dozen of metalens with random structure parameters as initial structures, the average focal depth of topology-shape optimized metalens is greatly improved up to 18.80 μm (about 29.7λ), which is 1.54 times higher than the diffraction-limited focal depth. Moreover, all the topology-shape optimized metalens exhibit high diffraction efficiency exceeding 0.7 over the whole focal depth range, which is approximately three times greater than that of the forward design. Our results offer a new insight into the design of extended depth-of-focus metalens and may find potential applications in imaging, holography, and optical fabrication.

In accordance with the principle that the cube graph can be obtained by superimposing planes, a multiple-image encryption scheme based on hyperchaotic map and 3D cube is designed in this paper. Multiple images are segmented by columns, and a regular cube is obtained by stacking multiple fixed-size planes. Each stacked plane is considered as a stacked plane of the cube along the z-axis direction. Firstly, each tangent plane is rotated by different angles in the counterclockwise direction and then DNA encoded, followed by face swap, row swap, and column swap in turn. Then, the DNA-encoded image cube is subjected to DNA addition with the chaotic cube. Finally, two DNA sequences are randomly selected for DNA mutation. The mutated cube is decoded into a digital cube by DNA and the multiple-image encryption algorithm is completed. Theoretically, the cube used in the encryption process can be infinitely large, which means that the number and the size of 2D images that can be encrypted can be unrestricted. Experimental simulations and performance tests prove that the proposed image encryption scheme is effective and secure.

Abstract Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.