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To study the damage power enhancement of fuel air explosive (FAE) with metal hydrides, the effects of metal hydrides (TiH2, MgH2, ZrH2) powders on shock wave and thermal damage of pure propylene oxide (PO) were explored using a 20 L spherical explosion test system combined with colorimetric thermometry technology. The experimental results showed that compared with the base metal powders, the explosion overpressures, maximum pressure rise rates and maximum average temperatures of the solid-liquid mixed fuel with the metal hydrides (TiH2, MgH2, ZrH2) powders increased by 11.04 %, 22.61 %, 4.80 % and 26.68 %, 38.18 %, 13.91 % as well as 6.85 %, 8.57 %, 1.34 %, respectively. Furthermore, the effects of metal hydride powders on the cloud explosion fuel were better than those of Al powders, and MgH2 powders had the most significant effects on the damage power enhancement of pure PO. Metal hydride powders as high-energy additives could improve the energy release characteristics of FAE.

Abstract Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-β-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.

Abstract Both cancer and fibrosis are diseases involving dysregulation of cell signaling pathways resulting in an altered cellular microenvironment which ultimately leads to progression of the condition. The two disease entities share common molecular pathophysiology and recent research has illuminated the how each promotes the other. Multiple imaging techniques have been developed to aid in the early and accurate diagnosis of each disease, and given the commonalities between the pathophysiology of the conditions, advances in imaging one disease have opened new avenues to study the other. Here, we detail the most up-to-date advances in imaging techniques for each disease and how they have crossed over to improve detection and monitoring of the other. We explore techniques in positron emission tomography (PET), magnetic resonance imaging (MRI), second generation harmonic Imaging (SGHI), ultrasound (US), radiomics, and artificial intelligence (AI). A new diagnostic imaging tool in PET/computed tomography (CT) is the use of radiolabeled fibroblast activation protein inhibitor (FAPI). SGHI uses high-frequency sound waves to penetrate deeper into the tissue, providing a more detailed view of the tumor microenvironment. Artificial intelligence with the aid of advanced deep learning (DL) algorithms has been highly effective in training computer systems to diagnose and classify neoplastic lesions in multiple organs. Ultimately, advancing imaging techniques in cancer and fibrosis can lead to significantly more timely and accurate diagnoses of both diseases resulting in better patient outcomes.

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.

Background Beat‐to‐beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure‐receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat‐to‐beat BPV within 24 hours of acute ischemic stroke onset. Methods and Results This study prospectively monitored beat‐to‐beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat‐to‐beat BPV, heart rate variability, and the cross‐correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat‐to‐beat BPV to the traditional model for predicting prognosis. Beat‐to‐beat BPV increased significantly in the unfavorable outcome group (P0.05). Furthermore, beat‐to‐beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P

Observations and models indicate that human activities exert a considerable impact on the frequency and intensity of extreme temperature events, which are associated with global warming. However, changes in the duration of extreme temperature events and their association with human influence have not been considered in most studies. Thus, the possible relationship between the observed changes in the warm and cold spell duration (WSDI and CSDI) in hotspot regions during 1960–2014 and human influence was investigated based on the NCEP/NCAR reanalysis version 1 and Coupled Model Inter-comparison Project Phase 6 (CMIP6) data. Constraint projection based on these attribution results was also performed. The optimal fingerprinting technique was used to compare observed changes in WSDI and CSDI to simulated changes averaged across eight CMIP6 models. Results show that anthropogenic (ANT) forcing contributed to the observed increase in WSDI in the three hotspot regions (West Asia, South Asia and Southeast Asia), with the majority of the changes being attributed to greenhouse gas forcing. However, a generally weak ANT signal can be observed in the decreasing trend of CSDI and can be detected in South and Southeast Asia. The influence of aerosol forcing remains undetected in either WSDI or CSDI, which differs from the results for frequency and intensity of extreme temperatures. The attribution results revealed that the constrained projection of WSDI is lower than the raw projection for 2015–2100 in West Asia and Southeast Asia. However, no differences in future CSDI changes are found in Southeast Asia between the constrained and raw projections.

An unbalanced protocol recognition method based on the improved Residual U-Net was proposed to solve the challenge of network security posed by the increasing network attacks with the continuous development of the Internet.In the captured network traffic, a small proportion is constituted by malicious traffic, typically utilizing minority protocols.However, existing protocol recognition methods struggle to accurately identify these minority protocols when the class distribution of the protocol data is imbalanced.To address this issue, an unbalanced protocol recognition method was proposed, which utilized the improved Residual U-Net, incorporating a novel activation function and the Squeeze-and-Excitation Networks (SE-Net) to enhance the feature extraction capability.The loss function employed in the proposed model was the weighted Dice loss function.In cases where the recognition accuracies of the minority protocols were low, the loss function value would be high.Consequently, the optimization direction of the model would be dominated by the minority protocols, resulting in improved recognition accuracies for them.During the protocol recognition process, the network flow was extracted from the network traffic and preprocessed to convert it into a one-dimensional matrix.Subsequently, the protocol recognition model extracted the features of the protocol data, and the Softmax classifier predicted the protocol types.Experimental results demonstrate that the proposed protocol recognition model achieves more accurate recognition of the minority protocols compared to the comparison model, while also improving the recognition accuracies of the majority protocols.

In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 μm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1–2.1 μm) and stage 3 (3.3–4.7 μm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.

Background: In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research focus in the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. This network meta-analysis aimed to systematically evaluate the efficacy and safety of CDK4/6 inhibitors combined with ET for HR+/HER2-breast cancer. Methods: A systematic search was conducted across PubMed, Web of Science, Cochrane Library, and GeenMedical databases to identify randomized controlled trials investigating the use of CDK4/6 inhibitors in combination with endocrine therapy for the treatment of HR+/HER2-breast cancer. The search period spanned from the inception of each database up to February 29, 2024. Data analysis was conducted using Stata 14.0 and R 4.1.0 software. Results: A total of 20 randomized controlled trials (RCTs) were included in this study, investigating the effectiveness of four CDK4/6 inhibitors—Abemaciclib, Dalpiciclib, Ribociclib, and Palbociclib—when combined with ET for the treatment of HR+/HER2-breast cancer. The results indicated that Abemaciclib + ET, Dalpiciclib + ET, Palbociclib + ET, and Ribociclib + ET exhibited similar therapeutic effects in terms of improving objective response rate (ORR), disease control rate (DCR) and reducing the occurrence of fatigue, all of which were superior to ET alone. However, in terms of prolonging progression-free survival (PFS) and overall survival (OS), Dalpiciclib + ET significantly improved PFS compared to Ribociclib + ET, Palbociclib + ET, Abemaciclib and Palbociclib. Ribociclib + ET significantly improved OS compared to Palbociclib + ET. Regarding overall adverse reaction events (AREs), Dalpiciclib + ET had a higher incidence compared to Ribociclib + ET. The incidence of neutropenia caused by Dalpiciclib + ET was significantly higher compared to Palbociclib + ET, Ribociclib + ET, Abemaciclib, and Palbociclib. Abemaciclib + ET demonstrated the worst safety profile concerning diarrhea. Conclusion: Abemaciclib + ET likely represents the most effective option in terms of therapeutic effects, but it is prone to causing diarrhea and fatigue. On the other hand, Dalpiciclib + ET likely demonstrates the best efficacy in terms of PFS but exhibits the poorest safety profile, particularly in relation to neutropenia. Therefore, clinicians should exercise increased vigilance in monitoring and managing adverse effects when prescribing Abemaciclib + ET and Dalpiciclib + ET.

Background: Remimazolam, a new ultrashort-acting benzodiazepine, is becoming increasingly applied in general anesthesia. This study is designed to investigate the effect of remimazolam-based total intravenous anesthesia and sevoflurane-based inhalation anesthesia on emergence delirium in pediatric tonsillectomy and adenoidectomy.Methods and analysis: This is a monocentric, prospective, randomized, double-blind clinical trial. A total of 90 pediatric patients will be randomized to receive remimazolam-based total intravenous anesthesia (remimazolam group, n = 45) or sevoflurane-based inhalation anesthesia (sevoflurane group, n = 45). The primary outcome will be the incidence of emergence delirium, which will be evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes include the extubation time, recovery time, behavior change using the post-hospitalization behavior questionnaire for ambulatory surgery (PHBQ-AS), and adverse events.Ethics and dissemination: This study has been approved by the Institutional Review Board (IRB) of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (2023-K-262-02).Clinical trial registration:ClinicalTrials.gov, identifier NCT06214117.

A launching system with a filter cartridge structure was proposed to improve the muzzle velocity of the projectile. The combustion chamber of the launching system is divided into two fixed chambers, one is located in the breech chamber, and the other is arranged in the barrel. The breech chamber charge was ignited first, and the charges in the auxiliary chambers were ignited by the high-temperature, high-pressure combustible gas trailing the projectile. In this way, the combustible gas in the auxiliary chambers could compensate for the pressure drop caused by the movement of the projectile. The proposed device features the advantage of launching a projectile with high muzzle velocity without exceeding the maximum pressure in the chamber. In order to obtain some internal ballistic characteristics of the launch system, some critical structure, such as the length of the filter cartridge auxiliary charge, the combustion degree of the propellant in the chamber, and the length of the barrel, are discussed. The experimental results show that with the increased auxiliary charge length, a pressure plateau or even a secondary peak pressure can be formed, which is less than the peak pressure. The projectile velocity increased by 23.57%, 14.64%, and 7.65% when the diaphragm thickness was 0 mm, 1 mm, and 2 mm, respectively. The muzzle velocity of the projectile can be increased by 13.42% by increasing the length of the barrel. Under the same charge condition, with the increase of barrel length, the energy utilization rate of propellant increases by 28.64%.

Pachychoroid spectrum diseases(PSD)have been defined as a group of diseases with similar choroidal features and pathological processes, such as central serous chorioretinopathy(CSC), polypoidal choroidal vasculopathy(PCV), etc. The main features are the changes in the thickness of vascular layers of the choroid and increasing vascular permeability. The development of modern ophthalmic imaging devices represented by optical coherence tomography angiography(OCTA)allowed intuitive investigation of the changes in the choroidal vascular layers, which gives a new insight into the pathogenesis of this spectrum diseases. This article summarizes the common clinical characteristics of healthy individuals and PSD and reviews the latest imaging findings. Whether each type of PSD is a phenotype of the same disease at different stages or other with similar characteristics was discussed from different perspectives, such as genetic background and anatomical structure, providing a reference for the study of pathogenesis, early clinical diagnosis, and prevention and treatment of this disease.

Abstract Background Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. Results A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. Conclusion In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.

Abstract To investigate the biological role and mechanism of circ_0084188 in colorectal cancer (CRC). Real‐time quantitative polymerase chain reaction and western blot assay were used to detect RNA levels and protein levels in CRC cell lines (HCT116 and SW480), respectively. Cell proliferation was evaluated by Cell Counting Kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, and colony formation assays. Cell apoptosis was determined using flow cytometry. Cell migration and invasion were measured by transwell assay. Sphere formation efficiency was determined by sphere formation assay. The interaction between microRNA‐654‐3p (miR‐654‐3p) and circ_0084188 or Kruppel‐like factor 12 (KLF12) was confirmed by a dual‐luciferase reporter, RNA immunoprecipitation and RNA pull‐down assays. Xenograft in CRC mice model was utilized for exploring the role of circ_0084188 in vivo.Circ_0084188 was overexpressed in CRC tissues and cells. Circ_0084188 silencing suppressed cell proliferation, migration, invasion, and stemness and induced apoptosis in CRC cells. Circ_0084188 acted as a sponge for miR‐654‐3p, and circ_0084188 regulated CRC cell behaviors via sponging miR‐654‐3p. Moreover, KLF12 was a target of miR‐654‐3p, and miR‐654‐3p overexpression inhibited the malignant behaviors of CRC cells by downregulating KLF12. Mechanically, circ_0084188 sponged miR‐654‐3p to regulate KLF12 expression in CRC cells. In addition, circ_0084188 downregulation inhibited tumor growth in vivo.Circ_0084188 knockdown might repress CRC progression partially via regulating the miR‐654‐3p/KLF12 axis, providing a novel insight into the pathogenesis of CRC.

Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.

Abstract Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum.

Abstract Background CD24+CK19+/CD24+SOX9+ resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed. Results The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues. tdTom+ hepatocytes were isolated from ROSA26 tdTomato mice following AAV8-Tbg-Cre-mediated recombination, EpCAM+ biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and ALB/GFP−EpCAM− cells were isolated from Alb CreERT /R26 GFP mice. A cocktail of small molecules was used to convert the isolated cells into LPCs. These in vitro cultured LPCs with CD24 and SOX9 expression regained the ability to proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 (Lcn2) at high levels. Accordingly, endogenous Cd24a + Lcn2 + LPCs were identified by integration of sc-RNA-sequencing and pathological datasets of liver dysfunction which indicates that LPCs produced by ductular reactions might also originate from the resident LPCs. Transplantation of in-vitro cultured Cd24a + Lcn2 + LPCs into CCl4-induced fibrotic livers exacerbated liver damage and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response. Conclusions CD24+LCN2+ LPCs constituted the expanding ductular reaction and contributed to macrophage-mediated inflammation in chronic liver damage. The current findings highlight the roles of LPCs from distinct origins and expose the possibility of targeting LPCs in the treatment of chronic hepatic diseases. Graphical Abstract

Peripheral retinal degeneration is a typical lesion in ophthalmic clinical practice. Each type of degeneration affects distinct retinal layers and may lead to sight-threatening complications. Due to its specific location, where current ophthalmic imaging technologies have difficulties observing, the pathogenesis remains unclear despite previous works. This review outlines the characteristics of peripheral retinal degeneration by different wide-field imaging technologies, including ultra-wide field fundus imaging, wide field spectral domain optical coherence tomography, optical coherence tomography angiography and fundus fluorescein angiography, as well as new perspectives on their pathogenesis or pathological characteristics so as to provide new ideas for clinical diagnosis and management. Due to the small size of sample and the lack of prospective and long-term observation of multimodal imaging, it is still impossible to comprehensively evaluate the progression and risk of different types of degeneration. Therefore, it is expected that wide-field multimodal imaging technology will be more widely applied to study the mechanism of peripheral retinal degeneration and guide the clinical practice options.

ABSTRACT: Objectives: This study was conducted in Jilin Province to investigate the mechanism involved in the antibiotic resistance and pathogenicity of Klebsiella pneumoniae. Methods: Lung samples were collected from large-scale pig farms in Jilin Province. Antimicrobial susceptibility and mouse lethality assays were carried out. K. pneumoniae isolate JP20, with high virulence and antibiotic resistance, was chosen for whole-genome sequencing. The complete sequence of its genome was annotated, and the virulence and antibiotic resistance mechanism were analysed. Results: A total of 32 K. pneumoniae strains were isolated and tested for antibiotic resistance and pathogenicity. Among them, the JP20 strain showed high levels of resistance to all tested antimicrobial agents and strong pathogenicity in mice (lethal dose of 1.35 × 1011 CFU/mL). Sequencing of the multidrug-resistant and highly virulent K. pneumoniae JP20 strain revealed that the antibiotic resistance genes were mainly carried by an IncR plasmid. We speculate that extended-spectrum β-lactamases and loss of outer membrane porin OmpK36 play an important role in carbapenem antibiotic resistance. This plasmid contains a mosaic structure consisting of a large number of mobile elements. Conclusion: Through genome-wide analysis, we found that an lncR plasmid carried by the JP20 strain may have evolved in pig farms, possibly leading to multidrug resistance in the JP20 strain. It is speculated that the antibiotic resistance of K. pneumoniae in pig farms is mainly mediated by mobile elements (insertion sequences, transposons, and plasmids). These data provide a basis for monitoring the antibiotic resistance of K. pneumoniae and lay a foundation for an improved understanding of the genomic characteristics and antibiotic resistance mechanism of K. pneumoniae.

Abstract In the framework of nonrelativistic QCD, the excited doubly heavy baryons are thoroughly studied via the channel $$e^{+} e^{-}\rightarrow \langle QQ^{\prime }\rangle [n] \rightarrow \Xi _{QQ^{\prime }} +\bar{Q^{\prime }} +{\bar{Q}}$$ e + e - → ⟨ Q Q ′ ⟩ [ n ] → Ξ Q Q ′ + Q ′ ¯ + Q ¯ , which takes place at the collision energy Z-pole. $$Q^{(\prime )}$$ Q ( ′ ) represents b or c quark for the production of $$\Xi _{cc}$$ Ξ cc , $$\Xi _{bc}$$ Ξ bc , and $$\Xi _{bb}$$ Ξ bb , respectively. All of the intermediate diquark states $$\langle QQ'\rangle [n]$$ ⟨ Q Q ′ ⟩ [ n ] in P-wave, $$\langle cc\rangle [^{1}P_{1}]_{{\bar{\textbf{3}}}}$$ ⟨ c c ⟩ [ 1 P 1 ] 3 ¯ , $$\langle cc\rangle [^{3}P_{J}]_{{\textbf{6}}}$$ ⟨ c c ⟩ [ 3 P J ] 6 , $$\langle bc\rangle [^{1}P_{1}]_{{\bar{\textbf{3}}}/ {\textbf{6}}}$$ ⟨ b c ⟩ [ 1 P 1 ] 3 ¯ / 6 , $$\langle bc\rangle [^{3}P_{J}]_{{\bar{\textbf{3}}}/ {\textbf{6}}}$$ ⟨ b c ⟩ [ 3 P J ] 3 ¯ / 6 , $$\langle bb \rangle [^{1}P_{1}]_{{\bar{\textbf{3}}}}$$ ⟨ b b ⟩ [ 1 P 1 ] 3 ¯ , and $$\langle bb\rangle [^{3}P_{J}]_{{\textbf{6}}}$$ ⟨ b b ⟩ [ 3 P J ] 6 with $$J=0$$ J = 0 , 1, or 2, are taken into account. The cross sections and differential distributions, including the transverse momentum, rapidity, angular, and invariant mass, are discussed for the excited baryons production. We find that the contributions of $$\langle cc \rangle $$ ⟨ c c ⟩ , $$\langle bc \rangle $$ ⟨ b c ⟩ , and $$\langle bb \rangle $$ ⟨ b b ⟩ in P-wave are found to be 3.97 $$\%$$ % , 5.08 $$\%$$ % , and 5.89 $$\%$$ % , respectively, compared to S-wave. Supposing that all excited states can decay into the ground state 100%, the total events $$N_{\Xi _{cc}}=8.48 \times 10^{4-6}$$ N Ξ cc = 8.48 × 10 4 - 6 , $$N_{\Xi _{bc}}=2.26\times 10^{5-7}$$ N Ξ bc = 2.26 × 10 5 - 7 , and $$N_{\Xi _{bb}}=4.12 \times 10^{3-5}$$ N Ξ bb = 4.12 × 10 3 - 5 would be produced at the Super-Z Factory with a high luminosity up to $${{\mathcal {L}}} \simeq 10^{34-36}\textrm{cm}^{-2} \textrm{s}^{-1}$$ L ≃ 10 34 - 36 cm - 2 s - 1 .

IntroductionSoil salinity–alkalinity has emerged as a global problem affecting many ecosystems, including grassland. Plants evolve into different ecotypes to adapt to various environments. Leymus chinensis widely distributed in the eastern Eurasian steppe, has evolved into two main ecotypes: yellow–green(YG) and gray–green (GG). Studies on the adaption mechanisms of both ecotypes in response to saline–alkaline stress are limited.MethodsIn this study, the growth and physiological traits of ecotypes YG and GG in soils with different salinity–alkalinity levels—severe saline–alkaline soil (SS), moderate saline–alkaline soil (MS), and light saline–alkaline soil (LS)—were studied. After exposure to saline–alkaline stress for 15 months, the L. chinensis ecotypes exhibited significant differences in the growth characteristics.ResultsThe specific leaf area, individual tiller biomass, net photosynthetic rate, and potassium content of the two ecotypes under MS conditions were significantly higher than or similar to those under LS conditions. This indicates that L. chinensis showed a certain degree of tolerance to saline–alkaline environments under MS conditions. Saline–alkaline stress increased the tillers by 56% in GG and reduced them by 26% in YG, and did not alter the SLA and the number of individual tiller leaves of GG but reduced that of YG. Moreover, with increasing levels of saline–alkaline stress, ecotype GG exhibited an increase in net photosynthetic rate (Pn), while ecotype YG showed insignificant changes. Under SS, GG exhibited higher Pn and chlorophyll content than YG. Additionally, with the increase in the saline–alkaline stress level, the Na+ content increased, but GG exhibited a significantly lower Na+ content than YG. Conversely, the K+ and Ca2+ contents and the K+/Na+ and Ca2+/Na+ ratios decreased, but GG exhibited higher values than YG.DiscussionGG reduced Na+ by absorption by increasing tillers. Additionally, GG absorbed more K+ and Ca2+ ions, thereby maintaining higher K+/Na+ and Ca2+/Na+ ratios than YG under saline–alkaline stress. These adaptive strategies enable ecotype GG to grow and maintain normal physiological functions under high saline–alkaline stress. The findings of this study hold practical significance for enhancing the economic and ecological value of saline–alkaline grasslands.

Abstract Objectives The recommended treatment for limited‐stage small‐cell lung cancer (LS‐SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4–6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS‐SCLC who received either 6 cycles or 4–5 cycles of EP chemotherapy combined with TRT. Materials and Methods In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS‐SCLC patients who received 4–6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4–5 cycles. To assess overall survival (OS) and progression‐free survival (PFS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM). Results Among the 265 LS‐SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4–5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4–5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6–53.1 months) vs. 22.7 months (95% CI, 20.8–29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7–30.5 months) vs. 12.0 months (95% CI, 9.8–14.2 months), respectively, p = 0.006]. The two‐year and five‐year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4–5 cycles group, respectively. Conclusion Patients diagnosed with LS‐SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4–5 cycles.

Summary: There is currently no consensus on the optimal perioperative pain management strategy involving specific opioids. This study aims to compare the postoperative analgesia, the associated side effects between nalbuphine and morphine in children undergoing laparoscopic surgery. One hundred ninety children were randomly assigned to nalbuphine (0.2 mg/kg) or morphine (0.2 mg/kg). Nalbuphine’s analgesic effect was non-inferior to morphine, with similar total rescue analgesic consumption during PACU stay (0.03 ± 0.05mg vs. 0.04 ± 0.06 mg, p > 0.05). Nalbuphine group had a lower incidence of respiratory depression (RR ≤ 10/min) (4.8% vs. 38.6%, p

Abstract Background For patients with advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, the suggested course of action is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Even with a high disease control rate, a majority of patients develop acquired EGFR-TKIs resistance and eventually advance. To increase the benefits of treatment, clinical trials are increasingly exploring the value of EGFR-TKIs combined with angiogenesis inhibitors as a first-line treatment in advanced NSCLC carrying EGFR mutations. Method Using PubMed, EMBASE and Cochrane Library, to locate published full-text articles in print or online, a thorough literature search was done from the database's inception to February 2021. Additionally, oral presentation RCTs from ESMO and ASCO were obtained. We sifted out RCTs that used EGFR-TKIs along with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant NSCLC. ORR, AEs, OS, and PFS were the endpoints. Review Manager version 5.4.1 was used for data analysis. Results One thousand eight hundred twenty-one patients were involved in 9 RCTs. According to the results, combining EGFR-TKIs with angiogenesis inhibitors therapy prolonged PFS of advanced EGFR-mutation NSCLC patients on the whole [HR:0.65 (95%CI: 0.59~0.73, P

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

There are many unidentified microbes in polluted soil needing to be explored and nominated to benefit the study of microbial ecology. In this study, a taxonomic research was carried out on five bacterial strains which were isolated and cultivated from polycyclic aromatic hydrocarbons, and heavy metals polluted soil of an abandoned coking plant. Phylogenetical analysis showed that they belonged to the phyla Proteobacteria and Actinobacteria, and their 16S rRNA gene sequence identities were lower than 98.5% to any known and validly nominated bacterial species, suggesting that they were potentially representing new species. Using polyphasic taxonomic approaches, the five strains were classified as new species of the families Microbacteriaceae and Sphingomonadaceae. Genome sizes of the five strains ranged from 3.07 to 6.60 Mb, with overall DNA G+C contents of 63.57–71.22 mol%. The five strains had average nucleotide identity of 72.38–87.38% and digital DNA-DNA hybridization of 14.0–34.2% comparing with their closely related type strains, which were all below the thresholds for species delineation, supporting these five strains as novel species. Based on the phylogenetic, phylogenomic, and phenotypic characterizations, the five novel species are proposed as Agromyces chromiiresistens (type strain H3Y2-19aT = CGMCC 1.61332T), Salinibacterium metalliresistens (type strain H3M29-4T = CGMCC 1.61335T), Novosphingobium album (type strain H3SJ31-1T = CGMCC 1.61329T), Sphingomonas pollutisoli (type strain H39-1-10T = CGMCC 1.61325T), and Sphingobium arseniciresistens (type strain H39-3-25T = CGMCC 1.61326T). Comparative genome analysis revealed that the species of the family Sphingomonadaceae represented by H39-1-10T, H39-3-25T, and H3SJ31-1T possessed more functional protein-coding genes for the degradation of aromatic pollutants than the species of the family Microbacteriaceae represented by H3Y2-19aT and H3M29-4T. Furthermore, their capacities of resisting heavy metals and metabolizing aromatic compounds were investigated. The results indicated that strains H3Y2-19aT and H39-3-25T were robustly resistant to chromate (VI) and/or arsenite (III). Strains H39-1-10T and H39-3-25T grew on aromatic compounds, including naphthalene, as carbon sources even in the presence of chromate (VI) and arsenite (III). These features reflected their adaptation to the polluted soil environment.

Abstract Background The role of chemoradiotherapy in unresectable locally advanced pancreatic cancer is still unclear. Methods Data from patients with unresectable locally advanced pancreatic cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. Univariate and multivariate Cox regression analyses were conducted to identify the independent prognostic factors of survival. Propensity score matching was carried out to minimize the interference of confounding factors. Subgroup analysis was performed to screen the characteristics of patients who would benefit from chemoradiotherapy. Results A total of 5002 patients with unresectable locally advanced pancreatic cancer were included. Among them, 2423 (48.4%) received chemotherapy, and 2579 (51.6%) received chemoradiotherapy. The median overall survival of all patients was 11 months. Multivariate Cox analysis showed that age (p 2 cm, adenocarcinoma, mucinous adenocarcinoma and white race. Conclusions Chemoradiotherapy is highly recommended for patients with unresectable locally advanced pancreatic cancer.

Caproic acid is a value-added product that has many uses in the preservation and synthesis of bio-energy. It is obtained via reverse β-oxidation reaction using electron donors and acceptors through the process of carbon chain elongation. The short-chain fatty acids are converted to high-value medium-chain fatty acids (such as caproic acid with six carbon chains). To improve the production yield of caproic acid, it is essential to clarify the relationship between reductase and energy supply, as well as the appropriate range of influencing factors and their mechanism in the biosynthesis process. This review paper describes the mechanisms of carbon chain elongation with lactic acid and ethanol as electron donors. Excessive ethanol oxidation, methanogenesis, and the lactate–acrylate pathways were introduced as competitive pathways during electron donor oxidation, and the corresponding inhibition methods were also reviewed. The reductase supply relationship between electron donor oxidation and electron acceptor reduction during the reverse β oxidation was discussed. In addition, this study clarified the utilization of energy by anaerobic microorganisms during the biosynthesis of caproic acid and two types of ATP synthesis: substrate level phosphorylation and electron transport phosphorylation. Electron bifurcation in the reverse β oxidation (a phenomenon in which two electrons from the same molecule are separated and redox potential is converted into energy to drive thermodynamically adverse reactions) and the role of different electron bifurcations in the production of caproic acid were evaluated. The influence of pH on the production of caproic acid driven by different electron donors was analyzed from the perspectives of competitive pathways, the growth range of functional microorganisms, and product inhibition. Regulating the collaboration between different bacterial communities and exploiting product separation techniques may enhance the production of caproic acid, and this should be investigated in the future. The role of CO2 and H2 as headspace in reverse β oxidation was investigated from the perspectives of substrates, competitive pathways, and thermodynamics. Relevant studies of the CO2 loading rate and H2 partial pressure were also reviewed. The development and current status of bioelectrochemical enhancement in the synthesis of caproic acid were examined, with emphasis on the fixation of CO2. Future research should focus on synthesizing caproic acid using lactic acid as an electron donor and organic wastewater as a substrate by bioelectrochemistry. This review summarized the advantages and disadvantages of the biosynthesis of caproic acid, providing theoretical guidance on how to produce it and improve its yield.

Abstract Background Pulmonary hypertension (PH) is a devastating disease characterized by vasoconstriction and vascular remodeling, leading to right ventricular failure and death. PH is a common complication of chronic obstructive pulmonary disease (COPD). Accumulating evidence demonstrate that microRNAs participate in the pathobiology of PH in COPD patients. In this study, we aimed to evaluate the expression and function of microRNA-4640-5p (miR-4640-5p) in PH. Methods The mRNA and protein levels were determined by quantitative polymerase chain reaction (qPCR) and western blot, separately. Functional assays and western blot were performed to determine the effects of miR-4640-5p and NOS1 on cell growth, migration. Besides, the dual-luciferase reporter assays were used to validate miR-4640-5p and NOS1 interactions. Results We found that miR-4640-5p expression was significantly higher in the lung tissues of COPD-PH patients than in the healthy controls while higher expression of miR-4640-5p was correlated with more severe COPD-PH. By using pulmonary artery smooth muscle cell (PASMC) in in vitro assays, we demonstrated that inhibition of miR-4640-5p suppressed cell proliferation and migration of PASMC via regulating mTOR/S6 signaling. Bioinformatics analysis and validation experiments revealed that nitric oxide synthase 1 (NOS1) was a direct downstream target of miR-4640-5p. Overexpression of NOS1 partially antagonized the effect of miR-4640-5p in regulating PASMC cell proliferation and migration. In addition, our findings suggested that miR-4640-5p/NOS1 axis regulated mitochondrial dynamics in PASMCs. Furthermore, in the hypoxia-induced PH rat model, inhibition of miR-4640-5p ameliorated PH with reduced right ventricular systolic pressure and Fulton index. Conclusions miR-4640-5p regulates PH via targeting NOS1, which provides a potential diagnostic biomarker and therapeutic target for COPD-PH patients.

Abstract Through the interaction of Higgs with heavy quarks in standard model, we have systematically studied and predicted the production of excited doubly heavy baryons based on non-relativistic QCD theory. The decay widths, differential distributions, and major theoretical uncertainties of the excited doubly heavy baryons via the process $$H \rightarrow \langle QQ'\rangle [n] \rightarrow \Xi _{QQ'}+ \bar{Q'} + \bar{Q}$$ H → ⟨ Q Q ′ ⟩ [ n ] → Ξ Q Q ′ + Q ′ ¯ + Q ¯ are discussed in detail. The spin and color quantum number of the intermediate P-wave diquark state $$\langle QQ'\rangle [n]$$ ⟨ Q Q ′ ⟩ [ n ] can be $$\langle cc\rangle [^{1}P_{1}]_{\varvec{\bar{3}}}$$ ⟨ c c ⟩ [ 1 P 1 ] 3 ¯ , $$\langle cc\rangle [^{3}P_{J}]_{\varvec{6}}$$ ⟨ c c ⟩ [ 3 P J ] 6 , $$\langle bc\rangle [^{1}P_{1}]_{\varvec{\bar{3}}/ \textbf{6}}$$ ⟨ b c ⟩ [ 1 P 1 ] 3 ¯ / 6 , $$\langle bc\rangle [^{3}P_{J}]_{\varvec{\bar{3}}/ \textbf{6}}$$ ⟨ b c ⟩ [ 3 P J ] 3 ¯ / 6 , $$\langle bb \rangle [^{1}P_{1}]_{\varvec{\bar{3}}}$$ ⟨ b b ⟩ [ 1 P 1 ] 3 ¯ and $$\langle bb\rangle [^{3}P_{J}]_{\textbf{6}}$$ ⟨ b b ⟩ [ 3 P J ] 6 , with $$J=0, 1, 2$$ J = 0 , 1 , 2 . The contributions from all summed P-wave states can be about $$3.05\%$$ 3.05 % , $$3.23\%$$ 3.23 % and $$2.19\%$$ 2.19 % of the S-wave states for the production of $$\Xi _{cc}$$ Ξ cc , $$\Xi _{bc}$$ Ξ bc and $$\Xi _{bb}$$ Ξ bb , accordingly. Therefore, there will be about 0.41 $$\times 10^4$$ × 10 4 events of $$\Xi _{cc}$$ Ξ cc , 6.35 $$\times 10^4$$ × 10 4 events of $$\Xi _{bc}$$ Ξ bc and 0.28 $$\times 10^4$$ × 10 4 events of $$\Xi _{bb}$$ Ξ bb produced per year at the HL-LHC, and a smaller number of events would be produced at the CEPC or ILC but with a cleaner background to be measured by the experiments.

AIM: To study the effect of leech extract on the expression of vascular endothelial growth factor(VEGF)in retinoblastoma(WERI-RB-1 cells)and the related molecular mechanism.METHODS: WERI-RB-1 cells cultured in vitro were divided into control group, 0.04U/mL leech extract group and 0.08U/mL leech extract group. The control group was cultured with complete medium for 48h, and the leech extract group was cultured with 0.04 and 0.08U/mL drug-containing medium for 48h, respectively. The expression level of VEGF in conditioned medium of cell culture was detected by ELISA. The mRNA levels of hypoxia-inducible factor-1a(HIF-1a)and matrix metalloproteinase-9(MMP-9)were detected by RT-PCR. The expression levels of HIF-1a, MMP-9, phosphatidylinositol 3-kinase(PI3K)and human phosphorylated AKT(p-AKT)were detected by Western Blot.RESULTS: Compared with the control group, the expression of VEGF in the conditioned medium with the concentration of 0.04U/ mL and 0.08U/mL of leech extract was decreased(P

Background: Enhanced Recovery After Surgery (ERAS) has been used to improve surgical outcomes in recent years. However, its safety and efficacy in elderly patients with gastric cancer remain unclear. The aim of this study was to reveal the safety and efficacy of the ERAS protocol in elderly patients with gastric cancer. Methods: Elderly gastric cancer patients (age≥70 years) who underwent gastrectomy were divided into the ERAS group and the conventional group. Postoperative complications, postoperative hospital stay, hospitalization expenses, and readmission rates were compared between the two groups. Results: From December 2019 to January 2021, 100 eligible patients were enrolled in our study. All baseline data were balanced between the ERAS group and the conventional group. There was no significant difference in terms of complications (18% vs. 16%, P = 0.14) between the two groups. The most common complication was pneumonia. Four patients were observed in the conventional group and three patients in the ERAS group. The postoperative hospital stay was shorter in the ERAS group (8.2 vs. 10.4, P = 0.001). Conclusions: The ERAS protocol could be safely used in elderly gastric cancer patients undergoing gastrectomy and shorten postoperative hospital stay.

Existing protocol recognition methods cannot effectively extract the temporal and spatial characteristics of protocol data,which leads to low accuracy of protocol recognition.An application layer protocol recognition method based on one dimensional residual network and recurrent neural network is proposed.The proposed model consists of one dimensional preactivated residual network(PreResNet) and bidirectional gated recurrent neural network(BiGRU).The PreResNet is used to extract spatial characteristics of the protocol data,and the BiGRU is used to extract temporal characteristics of the protocol data.The attention mechanism is used to extract the key features related to protocol recognition to improve the accuracy of protocol recognition.The proposed method firstly extracts the application layer protocol data from network traffic,and the data is preprocessed and transformed into one dimensional vectors.Then the classification model is trained with the training data and a mature protocol recognition model is obtained.Finally,the trained classification model is used to identify the application layer protocols.Experimental results on public dataset ISCX2012 show that the proposed protocol recognition model has an overall accuracy of 96.87% and an average F value of 96.81%,which are higher than those of other protocol recognition models.

AbstractBeclin1 is a key regulator of a family of autophagy-related proteins. The aim of our study was to elucidate the clinicopathological and prognostic significance of Beclin1 expression which is a positive regulator of autophagy in cervical cancer. The results showed that a total of 2682 patients were enrolled in 21 case-control studies. The results showed that, as for Beclin1 expression, significant differences were found in cervical cancer vs. normal cervical tissues (p

Summary Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium sulfate, dextran gel chromatography column and Q‐Sepharose column chromatography successively. The molecular mass of bacteriocin PA166 was found to be 49.38 kDa by SDS‐PAGE and liquid chromatography–mass spectrometry (MS)/MS. Bacteriocin PA166 showed stability at a wide range of pH (2–10), and thermal stability (40, 60, 80 and 100°C). The bacteriocin PA166 antimicrobial activity was slightly inhibited by Ca2+, K+ and Mg2+. The minimum bactericidal concentrations of bacteriocin PA166 against five Pasteurella multocida strains ranged from 2 to 8 μg ml−1. Bacteriocin PA166 showed low cytotoxicity and a higher treatment index (TI = 82.51). Fluorescence spectroscopy indicated that bacteriocin PA166 destroyed the cell membrane to exert antimicrobial activity. In summary, bacteriocin PA166 had strong antibacterial activity, high TI and low toxicity, and hence could serve as a potential clinical therapeutic drug.

Abstract Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued “Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline”. Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette–Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Abstract Combining computer-aided design and computer numerical control (CNC) with global technical connections have become interesting topics in the manufacturing industry. A framework was implemented that includes point clouds to workpieces and consists of a mesh generation from geometric data, optimal surface segmentation for CNC, and tool path planning with a certified scallop height. The latest methods were introduced into the mesh generation with implicit geometric regularization and total generalized variation. Once the mesh model was obtained, a fast and robust optimal surface segmentation method is provided by establishing a weighted graph and searching for the minimum spanning tree of the graph for extraordinary points. This method is easy to implement, and the number of segmented patches can be controlled while preserving the sharp features of the workpiece. Finally, a contour parallel tool-path with a confined scallop height is generated on each patch based on B-spline fitting. Experimental results show that the proposed framework is effective and robust.