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Abstract Acne is a prevalent inflammatory disease in dermatology, and its pathogenesis may be associated with inflammation, immunity, and other mechanisms. It commonly manifests in young individuals and frequently imposes a heavy economic, physical, and psychological burden on patients. Gut microbes and blood metabolites, as significant immune and inflammatory regulators in the body, have been hypothesized to form the “neurocutaneous axis.” Nonetheless, the precise causal relationships among the gut microbes, circulating blood metabolites, and acne development have yet to be elucidated. This study employed bidirectional two-sample Mendelian randomization (MR) to probe the causal impacts of 412 distinct gut microbes and 249 blood metabolites on acne. Single nucleotide polymorphisms (SNPs), which are closely associated with gut microbes and blood metabolites, were utilized as instrumental variables. This approach was taken to discern whether these elements serve as pathogenic or protective factors in relation to acne. Furthermore, a mediation analysis encompassing gut microbes, blood metabolites, and acne was conducted to explore potential correlations between gut microbes and blood metabolites, as well as their cumulative effects on acne. This was done to substantiate the notion of causality. Bidirectional two-sample MR analysis revealed 8 gut bacteria, 6 bacterial metabolic abundance pathways determined by birdshot, and 8 blood metabolites significantly associated with acne. The mediation MR analysis revealed 2 potential causal relationships, namely, Bifidobacterium-DHA-Acne and Bifidobacterium-Degree of Unsaturation-Acne. This study identified gut microbes and blood metabolites that are causally associated with acne. A potential causal relationship between gut microbes and blood metabolites was obtained via mediation analysis. These insights pave the way for the identification of new targets and the formulation of innovative approaches for the prevention and treatment of acne.

Abstract TET2 is a critical gene that regulates DNA methylation, encoding a dioxygenase protein that plays a vital role in the regulation of genomic methylation and other epigenetic modifications, as well as in hematopoiesis. Mutations in TET2 are present in 7%–28% of adult acute myeloid leukemia (AML) patients. Despite this, the precise mechanisms by which TET2 mutations contribute to malignant transformation and how these insights can be leveraged to enhance treatment strategies for AML patients with TET2 mutations remain unclear. In this review, we provide an overview of the functions of TET2, the effects of its mutations, its role in clonal hematopoiesis, and the possible mechanisms of leukemogenesis. Additionally, we explore the mutational landscape across different AML subtypes and present recent promising preclinical research findings.

Abstract Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Abstract Background Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment.

Prenatal stress can lead to the programming of the neuroendocrine system in male offspring, disrupting the hypothalamic testicular axis and adversely affecting the reproductive health of male offspring. This study aimed to determine the long-term effects of prenatal stress on the KISS1 system in male offspring and the effects on reproductive function in male offspring. Sixteen pregnant females were divided into a prenatal control group (PC, n = 8) and a prenatal stress group (PS, n = 8). The PS group was modeled with chronic unpredictable mild stress (CUMS) from day 1 of gestation to full-term delivery. Differences between the two groups in various maternal parameters, including glucocorticoid secretion, litter size, and the effects of male offspring birth weight, the KISS1 system, and reproductive function, were determined. Male offspring of PS dams had lower birth weights compared to prenatal controls. KISS1 gene expression is reduced at birth and in adult PS offspring, and its receptor KISS1-R protein is similarly reduced in PS offspring at birth and adulthood. In adulthood, PS male offspring show significantly reduced sex hormone production, altered testicular morphology, reduced maturation of their supporting cells, and decreased expression of connexin 43 (CX43), leading to an altered sperm microenvironment and reduced sperm quality. In conclusion, prenatal stress leads to adverse changes in the KISS1 system in male offspring and decreased reproductive function.

Abstract Abnormal SUMOylation is implicated in non-alcoholic fatty liver disease (NAFLD) progression. Forkhead box protein A1 (FoxA1) has been shown to protect liver from steatosis, which was down-regulated in NAFLD. This study elucidated the role of FoxA1 deSUMOylation in NAFLD. NAFLD models were established in high-fat diet (HFD)-induced mice and palmitate acid (PAL)-treated hepatocytes. Hepatic steatosis was evaluated by biochemical and histological methods. Lipid droplet formation was determined by BODIPY and Oil red O staining. Target molecule levels were analyzed by RT-qPCR, Western blotting, and immunohistochemistry staining. SUMOylation of FoxA1 was determined by Ni-NTA pull-down assay and SUMOylation assay Ultra Kit. Protein interaction and ubiquitination were detected by Co-IP. Gene transcription was assessed by ChIP and dual luciferase reporter assays. Liver FoxA1 knockout mice developed severe liver steatosis, which could be ameliorated by sirtuin 6 (Sirt6) overexpression. Nutritional stresses reduced Sumo2/3-mediated FoxA1 SUMOylation at lysine residue K6, which promoted lipid droplet formation by repressing fatty acid β-oxidation. Moreover, Sirt6 was a target gene of FoxA1, and Sirt6 transcription activity was restrained by deSUMOylation of FoxA1 at site K6. Furthermore, nutritional stresses-induced deSUMOylation of FoxA1 promoted the ubiquitination and degradation of FoxA1 with assistance of murine double minute 2 (Mdm2). Finally, activating FoxA1 SUMOylation delayed the progression of NAFLD in mice. DeSUMOylation of FoxA1 at K6 promotes FoxA1 degradation and then inhibits Sirt6 transcription, thereby suppressing fatty acid β-oxidation and facilitating NAFLD development. Our findings suggest that FoxA1 SUMOylation activation might be a promising therapeutic strategy for NAFLD.

In this research, we report fabrication of AZ91 (Mg–Al–Mn–Zn) matrix composites reinforced with a hybrid of hexagonal boron nitride nanoplatelets (BNNP) and nanotubes (BNNT) using spark plasma sintering (SPS) and hot isostatic pressing (HIP). The resultant composites present dense microstructure featured by the refined α-Mg grains decorated with eutectic along the α-Mg grain boundaries, and trace amounts of in-situ interfacial-reaction products such as Mg3N2 and MgB2 are observed to serve as chemical anchors for stronger interface. More importantly, the AZ91 composites reinforced with a hybrid of 0.4 wt% BNNPs-0.1 wt% BNNTs displays ∼209 MPa of compressive yield strength, ∼329 MPa of ultimate compressive strength and ∼19.4% of elongation, achieving satisfactory balance of strength and ductility when compared to the AZ91 composite reinforced with sole BNNPs. This improvement can be attributed to the unique three-dimensional hybrid structure, where BNNPs maintain their high specific surface area, and the de-bundled BNNTs extend like tentacles, further contributing to their interfacial adhesion with the matrix. This research is expected to pave the way for the development of Mg-based composites with an optimal balance of strength and ductility.

Degradable and high-barrier plastic packaging materials draw more attention with the development of a social economy and the demands of environmental protection. In this study, poly(propylene carbonate phthalate) (PPC-P) and poly(butylene adipate-co-terephthalate) (PBAT) blends with different ratios were designed and prepared, marked as PPC-P/PBAT. Chain extenders were introduced into the blends, and the mechanical properties, thermal properties, and barrier properties of the composites were studied. The 75PPC-P/PBAT with 2% extenders represent the best performance. The addition of the chain extender has significantly improved the thermal stability and tensile elongation of PPC-P/PBAT. On this basis, the PPC-P/PBAT composite film was coated with PVA and borax using the dipping and pulling method. The oxygen barrier properties have been further improved for the composite film with a coating layer. Considering the characteristics of biodegradability and a high-barrier property, the 75PPC-P/PBAT/2MDI@Gly blend coated with 2 wt% PVA and 3 wt% borax exhibits potential as a superior food/pharmaceutical plastic packaging material with excellent tensile and barrier properties.

Abstract Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring. We assessed histomorphological indices, including cerebellar Nissl staining, and Calbindin staining, and hippocampal hematoxylin and eosin staining. Furthermore, we observed the transmission of linoleic acid, enriched in sunflower seeds, to offspring through lactation. The oral administration of linoleic acid-rich sunflower seed oil by lactating mothers significantly prolonged the survival time of hyperbilirubinemic offspring mice. Mechanistically, linoleic acid counteracts the bilirubin-induced accumulation of ubiquitinated proteins and neuronal cell death by activating autophagy. Collectively, these findings elucidate the novel role of a maternal linoleic acid-supplemented diet in promoting child health.

Advanced metastatic cardia cancer is an intractable malignance with poor prognosis. It is often accompanied by upper digestive tract obstruction, which seriously affects the quality of patients. Therefore, effective relief of eating obstruction is an important goal in the treatment of cardia cancer. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in cardia cancer, but only a small percentage of patients will benefit from them due to immune resistance. Oncolytic viruses have been shown to enhance the efficacy of ICIs by altering the immune microenvironment. This indicates that oncolytic virus has the potential value of overcoming the immune resistance of cardia cancer. Here, we present a case with local recurrent and multiple metastatic cardia cancer accompanied by eating obstruction. After 4 cycles of chemotherapy plus ICI therapy, the patient´s metastases were significant shrink, but the recurrent carida lesion were almost unchanged. Then we implemented exploratory local injection of recombinant human adenovirus type 5(H101) into recurrent cardia lesion by painless gastroscopy. Surprisingly, the cardia lesion shrank significantly, and the eating obstruction was greatly relieved. We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment.

Dermatomyositis (DM) positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, mainly when linked with rapidly progressive interstitial lung disease (RP-ILD), is considered a refractory disease. Our report describes a critical case of clinically amyopathic dermatomyositis (CADM) with RP-ILD that tested positive for both anti-MDA5 and anti-Ro-52 antibodies. The patient showed a limited response to a combined therapy regimen of prednisone, iguratimod, and tacrolimus. However, after adjunct therapy with mycophenolate mofetil (MMF), the patient’s condition was controlled, his serum KL-6 levels decreased, and anti-MDA5 antibodies became negative. During the 68-week follow-up, the patient’s condition remained stable, with a satisfactory quality of life. This report also discusses the potential role of inflammatory cytokines in the pathophysiology of CADM and RP-ILD. Further research is required to confirm these results and investigate the application of MMF in maintenance therapy for CADM-associated RP-ILD.

Abstract Bile microecology changes play an important role in the occurrence and development of choledocholithiasis. At present, there is no clear report on the difference of bile microecology between asymptomatic patients with gallbladder polyps and choledocholithiasis. This study compared bile microecology between gallbladder polyp patients and patients with choledocholithiasis to identify risk factors for primary choledocholithiasis. This study was conducted in 3 hospitals in different regions of China. Bile samples from 26 patients with gallbladder polyps and 31 patients with choledocholithiasis were collected by laparoscopic cholecystectomy and endoscopic retrograde choledocholithiasis cholangiography (ERCP), respectively. The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. The α-diversity of bile microecological colonies was similar between gallbladder polyp and choledocholithiasis, but the β-diversity was different. Firmicutes, Proteobacteri, Bacteroidota and Actinobacteriota are the most common phyla in the gallbladder polyp group and choledocholithiasis group. However, compared with the gallbladder polyp patients, the abundance of Actinobacteriota has significantly lower in the choledocholithiasis group. At the genera level, the abundance of a variety of bacteria varies between the two groups, and Enterococcus was significantly elevated in choledocholithiasis group. In addition, bile biofilm formation—Pseudomonas aeruginosa was more metabolically active in the choledocholithiasis group, which was closely related to stone formation. The analysis of metabolites showed that a variety of metabolites decreased in the choledocholithiasis group, and the concentration of beta-muricholic acid decreased most significantly. For the first time, our study compared the bile of gallbladder polyp patients with patients with choledocholithiasis, and suggested that the change in the abundance of Actinobacteriota and Enterococcus were closely related to choledocholithiasis. The role of Pseudomonas aeruginosa biofilm in the formation of choledocholithiasis was discovered for the first time, and some prevention schemes for choledocholithiasis were discussed, which has important biological and medical significance.

This article focuses on analyzing the finite-time ruin probability within a specific class of discrete risk models. These models incorporate dependent claims, an interest rate component, and stationary noise terms exhibiting semi-heavy-tailed behavior. In this framework, the claim amount follows a unilateral linear dependent process with independent and identically distributed noise terms, while the discount factor is determined by both the interest rate and time. The finite-time ruin probability has been derived under insurance risk conditions resembling the gamma distribution.

Abstract Background Brown adipose tissue (BAT) is known to be capable of non-shivering thermogenesis under cold stimulation, which is related to the mortality of animals. In the previous study, we observed that goat BAT is mainly located around the kidney at birth, and changes to white adipose tissue (WAT) in the perirenal adipose tissue of goats within one month after birth. However, the regulatory factors underlying this change is remain unclear. In this study, we systematically studied the perirenal adipose tissue of goat kids in histological, cytological, and accompanying molecular level changes from 0 to 28 d after birth. Results Our study found a higher mortality rate in winter-born goat kids, with goat birthing data statistics. Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d. This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids. Additionally, we found a series of changes of BAT during the first 28 d after birth, such as whitening, larger lipid droplets, decreased mitochondrial numbers, and down-regulation of key thermogenesis-related genes (UCP1, DIO2, UCP2, CIDEA, PPARGC1a, C/EBPb, and C/EBPa). Then, we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats. Furthermore, 12 candidate genes were found to potentially regulate goat BAT thermogenesis. The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes. While apoptosis may play a limited role, it is largely not critical in this transition process. Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids, with notable species differences in the expression of adipose tissue marker genes, and we highlighted some potential marker genes for goat BAT and WAT. Additionally, the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.

Background: The majority of HR+/HER2-breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2-breast cancer after neoadjuvant chemotherapy. Methods: We analyzed HR+/HER2-breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3–5 and positive lymph node ratio of ≤10 %, was used as a pathological evaluation indicator. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. Results: From January 2010 to December 2020, 386 patients were included in the final analysis. 28 patients (7.3 %) achieved pCR and 118 patients (30.6 %) achieved MPR. The median duration of follow-up was 54.4 months,5-year EFS was 87 % in the MPR group vs. 68 % in the non-MPR group. Multivariate analysis showed that low PR expression, high clinical stage, lower Miller–Payne grades and Positive lymph node ratio were independent poor prognostic factors for EFS (all P values

Abstract Practical high‐voltage lithium metal batteries hold promise for high energy density applications, but face stability challenges in electrolytes for both 4 V‐class cathodes and lithium anode. To address this, we delve into the positive impacts of two crucial moieties in electrolyte chemistry: fluorine atom (‐F) and cyano group (‐CN) on the electrochemical performance of polyether electrolytes and lithium metal batteries. Cyano‐bearing polyether electrolytes possess strong solvation, accelerating Li+ desolvation with minimal SEI impact. Fluorinated polyether electrolytes possess weak solvation, and stabilize the lithium anode via preferential decomposition of F‐segment, exhibiting nearly 6000‐h stable cycling of lithium symmetric cell. Furthermore, the electron‐withdrawing properties of ‐F and ‐CN groups significantly bolster the high‐voltage tolerance of copolymer electrolyte, extending its operational range up to 5 V. This advancement enables the development of 4 V‐class lithium metal batteries compatible with various cathodes, including 4.45 V LiCoO2, 4.5 V LiNi0.8Co0.1Mn0.1O2, and 4.2 V LiNi0.5Co0.2Mn0.3O2. These findings provide insights into design principles centered around polymer components for high‐performance polymer electrolytes.

BackgroundGeneralized pustular psoriasis (GPP) is a severe type of psoriasis. The current treatment primarily relies on corticosteroids and immunosuppressants. In recent years, biologics have been increasingly utilized in the treatment of this disease, and have demonstrated good clinical efficacy. However, children and adolescents are primarily treated with immunosuppressants, which have limited clinical application due to the serious side effects they may cause. At the same time, the effectiveness of current treatments is unsatisfactory. Secukinumab has been widely reported to be effective and safe in treating this disease. However, there are still insufficient data on its use in treating GPP in children.ObjectiveTo conduct a systematic review of the existing literature on the use of secukinumab for treating generalized pustular psoriasis in children and adolescents, and to evaluate its clinical effectiveness and safety.MethodsWe conducted a systematic review of all the literature reporting on the treatment of GPP in children and adolescents with secukinumab.ResultsA total of 7 papers (46 patients) were included in this study. After 12 weeks of treatment, all 46 participants were able to achieve a GPPASI score of 90 or higher, with approximately 96% of patients achieving complete clearing of the lesions (GPPASI 100 or JDA0). Adverse events were reported in 8 patients, the rate of adverse reactions was approximately 17%.ConclusionThe treatment of GPP in children and adolescents with secukinumab has a rapid onset of action and a high safety profile. However, the results of the literature may be influenced by publication bias.

Abstract Polymeric binders account for only a small part of the electrodes in lithium‐ion batteries, but contribute an important role of adhesion and cohesion in the electrodes during charge/discharge processes to maintain the integrity of the electrode structure. Therefore, polymeric binders have become one of the key materials to improve the charge/discharge properties of lithium‐ion batteries. Qualified polymer binders should not only require good bond strength, mechanical properties, conductivity, chemical functionality and processing performance, but also be environmentally friendly and low cost. The existing commercial polymeric binders cannot meet all the above requirements at the same time. This is a hot research area that researchers are keen to focus on, and it is hoped that through structural design, the matching of functional groups can meet the requirements of high‐capacity lithium‐ion batteries with long cycle life. Focusing on the structural design of polymer binders, the mechanism of interaction with electrode materials, and the functional properties of polymer binders, this review summarizes the polymer binders used in the cathode and anode in recent years. It could expect that this review can inspire a deep consideration on these critical issues, paving new pathways to improve comprehensive performance of polymer binders.

Although triblock polycarbonate thermoplastic elastomers (TPEs) have recently attracted great interests due to their biodegradability, insufficient attentions have been paid to improving the elastomeric properties. Through a tandem reaction strategy involving CO2 / allyl glycidyl ether (AGE) / cyclohexene oxide (CHO), poly(cyclohexene carbonate)-b-poly(allyl glycidyl ether carbonate)-b-poly(cyclohexene carbonate) (PCAC) is successfully synthesized using a metal-free Lewis acid-base pair catalyst. The synthesized PCACs are pure well-defined ABA triblock all-polycarbonate, which is supported by 1H NMR, gel permeation chromatography (GPC), and diffusion-ordered spectroscopy (DOSY). A simple modification by grafting alkylthiol chains to PCAC results in excellent TPEs named PCAC-g-S-CaH2a+1 (PCASaC). The synthesized TPEs are characterized by atomic force microscopy (AFM), thermogravimetric analysis (TG), differential scanning calorimetry (DSC), and mechanical test. They demonstrate a semi-network and semi-domain phase separation structure, wide service temperature range, good strength, high elongation, and extremely high elastic recovery properties. This low-cost, biodegradable, high-performance TPE shows great potential for applications in biomedical, wearable products, sports equipment, and other fields.

Anticoagulant related nephropathy (ARN) is the result of glomerular hemorrhage in patients on systemic anticoagulation therapy or underlying coagulopathy. Red blood cells (RBC) that passed through the glomerular filtration barrier form RBC casts in the tubules, increase oxidative stress and result in acute tubular necrosis (ATN). The mechanisms of ARN still not completely discovered. Plasminogen activator inhibitor-1 (PAI-1) plays a significant role in the maintenance of coagulation homeostasis. We developed an animal model to study ARN in 5/6 nephrectomy (5/6NE) rats. The aim of this study was to elucidate the role of PAI-1 in the ARN pathogenesis. 5/6NE rats were treated per os with warfarin (0.75 mg/kg/day) or dabigatran (150 mg/kg/day) alone or in combination with PAI-1 antagonist TM5441 (2.5, 5.0 and 10 mg/kg/day). TM5441 in a dose dependent manner ameliorated anticoagulant-induced increase in serum creatinine in 5/6NE rats. Anticoagulant-associated increase in hematuria was no affected by TM5441. The levels of reactive oxygen species (ROS) in the kidneys were in a dose-dependent manner decreased in 5/6NE rats treated with an anticoagulant and TM5441. Our data demonstrates that PAI-1 may reduce ARN by decreasing ROS in the kidneys. Glomerular hemorrhage is not affected by anti-PAI-1 treatment. These findings indicate that while symptoms of ARN can be reduced by PAI-1 inhibition, the main pathogenesis of ARN – glomerular hemorrhage – cannot be prevented.

Abstract Background Reportedly, the stress–hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community‐dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all‐cause mortality in the community‐dwelling population. Methods A total of 18 480 participants were included out of 82 091 from the NHANES 1999–2014 survey. The Kaplan–Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log‐rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all‐cause mortality. A subgroup analysis was also conducted. Results A total of 3188 deaths occurred during a median follow‐up period of 11.0 (7.7; 15.4) years. The highest risk for all‐cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log‐rank p

BackgroundBreast cancer is a significant public health issue, exhibiting the most pronounced occurrence and fatality rates among malignant neoplasms globally. Targeted therapy is a medical intervention that focuses on specific molecular markers. This study aims to investigate and evaluate the current research trends and directions in the field of targeted therapy for breast cancer using bibliometric analysis.MethodThe Web of Science database was utilized to retrieve relevant articles published between 2003 and 2022. The VOSviewer software and Bibliometrix package in the R language were employed to conduct co-occurrence and clustering analyses of authors, countries, institutions, journals, references, and the CiteSpace tool was utilized for keyword burst detection.ResultsA total of 2,258 articles were included and the annual number of publications increased rapidly. The most prolific country on this topic was the USA (n=898, 39.77%) and the University of Texas MD Anderson Cancer Center published most papers (n=93). Dennis J. Slamon and Gabriel N. Hortobagyi stood out in the field, with Dennis J. Slamon leading in terms of co-citations(n=653) and Gabriel N. Hortobagyi topping the list in terms of published articles(n=18). The most productive journal was Breast Cancer Research and Treatment and the most cited journal was Journal of Clinical Oncology. The clustering of keywords indicated that the primary focus of researches in the past two decades was on the development and clinical evaluation of tumor-targeted drugs associated with the epidermal growth factor receptor (EGFR) family signaling pathway, and explored mechanisms related to biological behavior of breast cancer. Keywords co-occurrence and burst analysis identified current research hotspots and potential research trends.ConclusionThis study employed bibliometric analysis to examine research on targeted therapy for breast cancer over a span of 20 years, and identified development trends of research and elucidated potential research trajectories in the domain of this topic. This study helps in the identification of prospective collaborators and partner institutions for researchers.

Abstract Dissipative Kerr-soliton combs are laser pulses regularly sustained by a localized solitary wave on top of a continuous-wave background inside a nonlinear resonator. Usually, the intrinsic interactions between the background light and solitons are weak and localized. Here, we demonstrate a strong interaction between the generated soliton comb and the background light in a Brillouin-Kerr microcomb system. This strong interaction enables the generation of a monostable single-soliton microcomb on a silicon chip. Also, new phenomena related to soliton physics including solitons hopping between different states as well as controlling the formations of the soliton states by the pump power, are observed owing to such strong interaction. Utilizing this monostable single-soliton microcomb, we achieve the 100% deterministic turnkey operation successfully without any feedback controls. Importantly, it allows to output turnkey ultra-low-noise microwave signals using a free-running pump.

Abstract Purpose The status of hormone receptors (HR) is an independent factor affecting survival and chemotherapy sensitivity in breast cancer (BC) patients, with estrogen receptor (ER) and progesterone receptor (PR) having the most significant effects. The ER-/PR + phenotype has been controversial in BC, and experts will face many challenges in determining treatment strategies. Herein, we systematically analyzed the clinicopathological characteristics of the ER-/PR + phenotype in BC patients and the response to chemotherapy. Patients and methods We included two cohorts. The first cohort counted the relationship between clinicopathologic data and survival outcomes for 72,666 female patients in the Surveillance, Epidemiology, and End Results (SEER) database. The second cohort analyzed the relationship between clinicopathological data and pathologic complete response (pCR) rate in 879 patients at the Harbin Medical University Cancer Hospital. The classification data were compared by the chi-square test and Fister's exact test of the Logistic regression model, and predictor variables with P

Abstract The Gabija system is a newly discovered bacterial immune system that consists of GajA and GajB. Here we report the cryo-EM structure of the Gabija complex from Bacillus cereus VD045 at 3.6 Å, which provides the direct evidence of interactions between GajA and GajB. The Gabija complex is an octameric ring structure with four GajA and four GajB. GajA is an OLD nucleases family protein, while GajB belongs to the SF1 helicases. The Gabija complex has sequence-specific DNA nuclease activity and prefers circular rather than linear DNA as substrate, its activity is more sensitive to concentrations change of nucleotides compared to GajA alone. Our data suggest a mechanism of Gabija immunity: the nuclease activity of Gabija complex is inhibited under physiological conditions, while it is activated by depletion of NTP and dNTP upon the replication and transcription of invading phages and cleave the circular DNA to prevent phage DNA replication.

AbstractSepsis is still the leading cause of death as a result of infection. Metabolic disorder plays a vital role in sepsis progression. Glycolysis intensification is the most characteristic feature of sepsis-related metabolic disorders. The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a critical engine that controls the rate of glycolysis. Recent studies have revealed that sepsis accelerates the rate of PFKFB3-driven glycolysis in different cells, including macrophages, neutrophils, endothelial cells and lung fibroblasts. Furthermore, increased PFKFB3 is closely related to the excessive inflammatory response and high mortality in sepsis. Interestingly, inhibition of PFKFB3 alone or in combination has also shown great potential in the treatment of sepsis. Therefore, an improved understanding of the canonical and noncanonical functions of PFKFB3 may provide a novel combinatorial therapeutic target for sepsis. This review summarizes the role of PFKFB3-driven glycolysis in the regulation of immunocyte activation and nonimmune cell damage in sepsis. In addition, we present recent achievements in the development of PFKFB3 drugs and discuss their potential therapeutic roles in sepsis.KEY MESSAGESepsis induces high expression of PFKFB3 in immunocytes and nonimmune cells, thereby enhancing cellular glycolytic flux.PFKFB3-driven glycolysis reprogramming is closely related to an excessive inflammatory response and high mortality in sepsis.Inhibition of PFKFB3 alone or in combination provides a novel combinatorial therapeutic target for sepsis.

A series of CO2-based thermoplastic polyurethanes (TPUs) were prepared using CO2-based poly(polycarbonate) diol (PPCDL), 4,4′-methylenebis (cyclohexyl isocyanate) (HMDI), and polypropylene glycol (PPG and 1,4-butanediol (BDO) as the raw materials. The mechanical, thermal, optical, and barrier properties shape memory behaviors, while biocompatibility and degradation behaviors of the CO2-based TPUs are also systematically investigated. All the synthesized TPUs are highly transparent amorphous polymers, with one glass transition temperature at ~15–45 °C varying with hard segment content and soft segment composition. When PPG is incorporated into the soft segments, the resultant TPUs exhibit excellent self-healing and shape memory performances with the average shape fixity ratio and shape recovery ratio as high as 98.9% and 88.3%, respectively. Furthermore, the CO2-based TPUs also show superior water vapor permeability resistance, good biocompatibility, and good biodegradation properties, demonstrating their pretty competitive potential in the polyurethane industry applications.

High-temperature proton exchange membrane fuel cells (HT-PEMFCs) have become one of the important development directions of PEMFCs because of their outstanding features, including fast reaction kinetics, high tolerance against impurities in fuel, and easy heat and water management. The proton exchange membrane (PEM), as the core component of HT-PEMFCs, plays the most critical role in the performance of fuel cells. Phosphoric acid (PA)-doped membranes have showed satisfied proton conductivity at high-temperature and anhydrous conditions, and significant advancements have been achieved in the design and development of HT-PEMFCs based on PA-doped membranes. However, the persistent issue of HT-PEMFCs caused by PA leaching remains a challenge that cannot be ignored. This paper provides a concise overview of the proton conduction mechanism in HT-PEMs and the underlying causes of PA leaching in HT-PEMFCs and highlights the strategies aimed at mitigating PA leaching, such as designing crosslinked structures, incorporation of hygroscopic nanoparticles, improving the alkalinity of polymers, covalently linking acidic groups, preparation of multilayer membranes, constructing microporous structures, and formation of micro-phase separation. This review will offer a guidance for further research and development of HT-PEMFCs with high performance and longevity.

This study aims to investigate the effect of rock types, i.e., granite, conglomerate rock, limestone, and crushing mechanism, i.e., Vertical Shaft Impact (VSI) crusher, Horizontal Shaft Impact (HSI) crusher, on the morphology of manufactured sands. By combining the 3D scanning and spherical harmonic analysis, the morphological parameters of manufactured sands such as elongation ratio (EL), flatness ratio (Fl), aspect ratio (AR), edge angle (EA), sphericity (SH), and fractal dimension were quantified. The results indicate limestone is more readily broken into blade-shaped particles without being able to blunt sharp edges through constant abrasion. The proportion of bladed particles in manufactured sand prepared from limestone is 1.91 times higher than the proportion of bladed particles in conglomerates. Additionally, the HSI crusher has a more significant effect on rocks with smaller strength. For the same parent rock, manufactured sand from a VSI crusher contains 30% more spherical and oblate particles than from an HSI crusher.

Aim: The current study evaluated the antibacterial activity of a newly developed quaternary ammonium polymethacrylate (QAPM)-containing bioactive glasses (BGs) via a two-step method by our group, namely BGs-HAEMB, and explored its cytotoxicity and biocompatibility. Methods: The antibacterial effects of the BGs-HAEMB against planktonic bacteria, bacterial biofilm formation, and experimental root canal biofilms of persistent pathogens (Enterococcus faecalis, Streptococcus sanguis and Porphyromonas endodontalis) associated with endodontic infection were evaluated in vitro by agar diffusion tests, direct contact tests and live/dead staining. The cytotoxicity and biocompatibility of BGs-HAEMB were evaluated by CCK-8 assays in vitro and a skin implantation model in vivo. Results: Compared to three clinically used endodontic sealers (Endofill, AH Plus, and iRoot SP), BGs-HAEMB exhibited the relatively strongest antibacterial effect against E. faecalis, S. sanguis and P. endodontalis after sitting for 14 and 28 days (P

Abstract Background Elastin-driven genetic diseases are a group of complex diseases driven by elastin protein insufficiency and dominant-negative production of aberrant protein, including supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. Here, a Chinese boy with a novel nonsense mutation in the ELN gene is reported. Case presentation We report a 1-year-old boy who presented with exercise intolerance, weight growth restriction with age, a 1-year history of heart murmur, and inguinal hernia. Gene sequencing revealed a novel nonsense mutation in the ELN gene (c.757 C > T (p.Gln253Ter), NM_000501.4). Due to severe branch pulmonary artery stenosis, the reconstruction of the branch pulmonary artery with autologous pericardium was performed. The inguinal hernia repair was performed 3 months postoperatively. After six months of outpatient follow-up, the child recovered well, gained weight with age, and had no special clinical symptoms. Conclusion We identified a de novo nonsense mutation in the ELN gene leading to mild SVAS and severe branch pulmonary artery stenosis. A new phenotype of inguinal hernia was also needed to be considered for possible association with the ELN gene. Still, further confirmation will be necessary.

Abstract Background 1H magnetic resonance spectroscopy (1H-MRS) can be used to study neurological disorders because it can be utilized to examine the concentrations of related metabolites. However, the diagnostic utility of different field strengths for temporal lobe epilepsy (TLE) remains unclear. The purpose of this study is to make quantitative comparisons of metabolites of TLE at 1.5T and 3.0T and evaluate their efficacy. Methods Our retrospective collections included the single-voxel 1H-MRS of 23 TLE patients and 17 healthy control volunteers (HCs) with a 1.5T scanner, as well as 29 TLE patients and 17 HCs with a 3.0T scanner. Particularly, HCs were involved both the scans with 1.5T and 3.0T scanners, respectively. The metabolites, including the N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were measured in the left or right temporal pole of brain. To analyze the ratio of brain metabolites, including NAA/Cr, NAA/Cho, NAA/(Cho + Cr) and Cho/Cr, four controlled experiments were designed to evaluate the diagnostic utility of TLE on 1.5T and 3.0T MRS, included: (1) 1.5T TLE group vs. 1.5T HCs by the Mann-Whitney U Test, (2) 3.0T TLE group vs. 3.0T HCs by the Mann-Whitney U Test, (3) the power analysis for the 1.5T and 3.0T scanner, and (4) 3.0T HCs vs. 1.5T HCs by Paired T-Test. Results Three metabolite ratios (NAA/Cr, NAA/Cho, and NAA/(Cho + Cr) showed the same statistical difference (p

Abstract Background Studies have shown that supplementation with recombinant human GH (rh-GH) during ovarian stimulation (OS) may improve the ovarian response and clinical outcomes of IVF. However, it remains unclear whether GH is associated with the ploidy status of embryos, and therefore, is unable to explain the underlying reason for the effect of GH on IVF outcomes. This study aimed to investigate whether GH supplementation in women with advanced maternal age (AMA) during OS is related to an increased probability of obtaining euploid blastocysts. Methods This was a single center retrospective cohort study. The data of all women aged 38–46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle between January 2021 and June 2022 were reviewed. Patients in the GH group received 4 IU/day subcutaneous GH supplementation from the beginning of OS to the trigger day, and patients in the control group did not. A total of 140 patients in the GH group and 272 patients in the control group were included after 1:2 propensity score matching. Results The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group than that in the control group (41.43% vs. 27.21%, P = 0.00). The GH group had a significantly higher euploid blastocyst rate per cohort (32.47% vs. 21.34%, P = 0.00) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.35 ± 0.40 vs. 0.21 ± 0.33, P = 0.00; per OS cycle 0.27 ± 0.38 vs. 0.16 ± 0.30, P = 0.02). However, the benefit of GH was more significant in patients aged 38–40 years, but not significant in patients aged 41–46 years. Pregnancy outcomes were similar between the two groups after embryo transfer. Conclusions GH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38–40 years, but this benefit is not significant in women aged 41–46 years. Our results explained the underlying reason for the effect of GH on IVF outcomes in existing studies, and might be helpful for AMA patients undergoing PGT-A cycles to obtain a better outcome meanwhile to avoid over-treatment. Trial registration NCT05574894, www.clinicaltrials.gov .

Abstract Nonlinear optics provides a means to bridge between different electromagnetic frequencies, enabling communication between visible, infrared, and terahertz bands through χ (2) and higher-order nonlinear optical processes. However, precisely modulating nonlinear optical waves in 3D space remains a significant challenge, severely limiting the ability to directly manipulate optical information across different wavelength bands. Here, we propose and experimentally demonstrate a three-dimensional (3D) χ (2)-super-pixel hologram with nanometer resolution in lithium niobate crystals, capable of performing advanced processing tasks. In our design, each pixel consists of properly arranged nanodomain structures capable of completely and dynamically manipulating the complex-amplitude of nonlinear waves. Fabricated by femtosecond laser writing, the nonlinear hologram features a pixel diameter of 500 nm and a pixel density of approximately 25000 pixels-per-inch (PPI), reaching far beyond the state of the art. In our experiments, we successfully demonstrate the novel functions of the hologram to process near-infrared (NIR) information at visible wavelengths, including dynamic 3D nonlinear holographic imaging and frequency-up-converted image recognition. Our scheme provides a promising nano-optic platform for high-capacity optical storage and multi-functional information processing across different wavelength ranges.

Vibration mixing, characterized by the high-frequency vibrations of the mixing shaft, can enhance the mechanical properties of ultra-high-performance concrete (UHPC). However, the effects of vibration mixing on carbon nanotube (CNT)-reinforced UHPC have not been previously reported. To investigate the impact of vibration mixing on the properties of CNT-reinforced UHPC, a comparative study was conducted using different vibration mixing durations and twin-shaft mixing. The results indicate that for CNT-reinforced UHPC, vibration mixing achieves better flowability, higher wet apparent density, and superior mechanical properties in shorter mixing times compared to twin-shaft mixing, making it a more favorable method. Considering vibration mixing times ranging from 3 to 7 min, the optimal time was found to be 3 min, during which the axial compressive strength increased by 3.3%, the elastic limit tensile strength and tensile strength improved by 14.6% and 15.8%, respectively, and the initial cracking strength and flexural strength increased by 12.6% and 13.4%, respectively, compared to values after 10 min of twin-shaft mixing.

To address the challenges posed by the narrow oxidation decomposition potential window and the characteristic of low ionic conductivity at room temperature of solid polymer electrolytes (SPEs), carbon dioxide (CO2), epichlorohydrin (PO), caprolactone (CL), and phthalic anhydride (PA) were employed in synthesizing di-block copolymer PCL-b-PPC and PCL-b-PPCP. The carbonate and ester bonds in PPC and PCL provide high electrochemical stability, while the polyether segments in PPC contribute to the high ion conductivity. To further improve the ion conductivity, we added succinonitrile as a plasticizer to the copolymer and used the copolymer to assemble lithium metal batteries (LMBs) with LiFePO4 as the cathode. The LiFePO4/SPE/Li battery assembled with PCL-b-PPC electrolyte exhibited an initial discharge-specific capacity of 155.5 mAh·g−1 at 0.5 C and 60 °C. After 270 cycles, the discharge-specific capacity was 140.8 mAh·g−1, with a capacity retention of 90.5% and an average coulombic efficiency of 99%, exhibiting excellent electrochemical performance. The study establishes the design strategies of di-block polymer electrolytes and provides a new strategy for the application of LMBs.

The light homogenizing element is a crucial component of the illumination system of the lithography machine. Its primary purpose is to realize the uniform distribution of energy. However, it suffers from a common issue, which is angular spectrum discreteness, which significantly impacts light uniformity. To address this, we design and fabricate random micro-cylindrical lens arrays to obtain a small-angle Gaussian optical field, which can compensate for the angular spectrum discreteness. By adjusting the pitches and curvature radii of the micro-cylindrical lenses separately, we are able to manipulate the divergence angle of the emitted sub-beams, enabling precise angular spectrum modulation. By using mask-moving technology, the angular spectrum modulator is fabricated to generate a Gaussian illumination field. The surface profile is measured and determined with a structural roughness below 10 nm. Furthermore, optical test experiments on the modulator have been conducted, achieving an angle error of less than 0.02° and a balance better than 0.5%.

High-energy-density Li-CO2 batteries are promising candidates for large-capacity energy storage systems. However, the development of Li-CO2 batteries has been hindered by low cycle life and high overpotential. In this study, we propose a CO2-based thermoplastic polyurethane (CO2-based TPU) with CO2 adsorption properties and excellent self-healing performance to replace traditional polyvinylidene fluoride (PVDF) as the cathode binder. The CO2-based TPU enhances the interfacial concentration of CO2 at the cathode/electrolyte interfaces, effectively increasing the discharge voltage and lowering the charge voltage of Li-CO2 batteries. Moreover, the CO2 fixed by urethane groups (-NH-COO-) in the CO2-based TPU are difficult to shuttle to and corrode the Li anode, minimizing CO2 side reactions with lithium metal and improving the cycling performance of Li-CO2 batteries. In this work, Li-CO2 batteries with CO2-based TPU as the multifunctional binders exhibit stable cycling performance for 52 cycles at a current density of 0.2 A g−1, with a distinctly lower polarization voltage than PVDF bound Li-CO2 batteries.

Fatigue cracking is one of the primary distresses of asphalt pavements, which significantly affects the asphalt pavement performance. The fatigue behavior of the asphalt mixture observed in the laboratory test can vary depending on the type of fatigue test and the dimension and shape of the test specimen. The variations can make it difficult to accurately evaluate the fatigue properties of the field asphalt concrete. Accordingly, this study proposed a reliable method to evaluate the fatigue behavior of the asphalt field cores based on discrete element modeling (DEM). The mesoscopic geometric model was built using discrete element software PFC (Particle Flow Code) and CT scan images of the asphalt field cores. The virtual fatigue test was simulated in accordance with the semi-circular bending (SCB) test. The mesoscopic parameters of the contacting model in the virtual test were determined through the uniaxial compression dynamic modulus test and SCB test. Based on the virtual SCB test, the displacement, contact forces, and crack growth were analyzed. The test results show that the fatigue life simulated in the virtual test was consistent with that of the SCB fatigue test. The fatigue cracks in the asphalt mixture were observed in three stages, i.e., crack initiation, crack propagation, and failure. It was found that the crack propagation stage consumes a significant portion of the fatigue life since the tensile contact forces mainly increase in this stage.

The binder ratio in a commercial lithium-ion battery is very low, but it is one of the key materials affecting the battery’s performance. In this paper, polycarbonate-based polymers with liner or chain extension structures are proposed as binders. Then, dry LiFePO4 (LFP) electrodes with these binders are prepared using the solvent-free method. Polycarbonate-based polymers have a high tensile strength and a satisfactory bonding strength, and the rich polar carbonate groups provide highly ionic conductivity as binders. The batteries with poly (propylene carbonate)-plus (PPC-P) as binders were shown to have a long cycle life (350 cycles under 1 C, 89% of capacity retention). The preparation of dry electrodes using polycarbonate-based polymers can avoid the use of solvents and shorten the process of preparing electrodes. It can also greatly reduce the manufacturing cost of batteries and effectively use industrial waste gas dioxide oxidation. Most importantly, a battery material with this kind of polycarbonate polymer as a binder is easily recycled by simply heating after the battery is discarded. This paper provides a new idea for the industrialization and development of a novel binder.

Poly(propylene carbonate-co-phthalate) (PPC-P) is an amorphous copolymer of aliphatic polycarbonate and aromatic polyester; it possesses good biodegradability, superior mechanical performances, high thermal properties, and excellent affinity with CO2. Hence, we fabricate PPC-P foams in an autoclave by using subcritical CO2 as a physical blowing agent. Both saturation pressure and foaming temperature affect the foaming behaviors of PPC-P, including CO2 adsorption and desorption performance, foaming ratio, cell size, porosity, cell density, and nucleation density, which are investigated in this research. Moreover, the low-cost PPC-P/nano-CaCO3 and PPC-P/starch composites are prepared and foamed using the same procedure. The obtained PPC-P-based foams show ultra-high expansion ratio and refined microcellular structures simultaneously. Besides, nano-CaCO3 can effectively improve PPC-P’s rheological properties and foamability. In addition, the introduction of starch into PPC-P can lead to a large number of open cells. Beyond all doubt, this work can certainly provide both a kind of new biodegradable PPC-P-based foam materials and an economic methodology to make biodegradable plastic foams. These foams are potentially applicable in the packaging, transportation, and food industry.

Lithium metal batteries (LMBs) are anticipated to meet the demand for high energy density, but the growth of lithium dendrites seriously hinders its practical application. Herein, we constructed a kind of composite separator (ZIF-90@PP) consisting of zeolite imidazole framework-90 (ZIF-90) and polypropylene (PP) to promote the uniform deposition of Li+ and inhibit the growth of lithium dendrites. The aldehyde groups interacting with TFSI− and the nitrogen-containing negative groups attracting Li+ of ZIF-90 can facilitate the dissociation of LiTFSI to release more Li+, thus alleviating the influence of space charge near the electrode surface and accelerating the transfer of Li+. Not only does the excellent electrolyte wettability of ZIF-90 enhance the electrolyte retention capacity of the separator, but the orderly nano-channels in ZIF-90 also restrict the free migration of anions and homogenize the distribution of Li+. Consequently, the functional separator achieves a long-term stable Li plating/stripping cycling for over 780 h at 2 mA cm−2. Moreover, an impressive average coulombic efficiency of 98.67% at 0.5 C after 300 cycles is realized by Li || LFP full cells based on ZIF-90@PP with a capacity retention rate of 71.22%. The high-rate and long cycling performance of the modified Li || LFP cells further demonstrates the advantages of the ZIF-90@PP composite separator.

Unmanned Aerial Vehicle (UAV) aerial sensors are an important means of collecting ground image data. Through the road segmentation and vehicle detection of drivable areas in UAV aerial images, they can be applied to monitoring roads, traffic flow detection, traffic management, etc. As well, they can be integrated with intelligent transportation systems to support the related work of transportation departments. Existing algorithms only realize a single task, while intelligent transportation requires the simultaneous processing of multiple tasks, which cannot meet complex practical needs. However, UAV aerial images have the characteristics of variable road scenes, a large number of small targets, and dense vehicles, which make it difficult to complete the tasks. In response to these issues, we propose to implement road segmentation and on-road vehicle detection tasks in the same framework for UAV aerial images, and we conduct experiments on a self-constructed dataset based on the DroneVehicle dataset. For road segmentation, we propose a new algorithm C-DeepLabV3+. The new algorithm introduces the coordinate attention (CA) module, which can obtain more accurate segmentation target location information and make the segmentation target edges more continuous. Also, the improved algorithm introduces the cascade feature fusion module to prevent the loss of detail information in road segmentation and to obtain better segmentation performance. For vehicle detection, we propose an improved algorithm S-YOLOv5 by adding a parameter-free lightweight attention module SimAM. Finally, the proposed road segmentation–vehicle detection framework is utilized to unite the C-DeepLabV3+ and S-YOLOv5 algorithms for the implementation of the serial tasks. The experimental results show that on the constructed ViDroneVehicle dataset, the C-DeepLabV3+ algorithm has an mPA value of 98.75% and an mIoU value of 97.53%, which can better segment the road area and solve the problem of occlusion. The mAP value of the S-YOLOv5 algorithm has an mAP value of 97.40%, which is more than YOLOv5’s 96.95%, which effectively reduces the vehicle omission and false detection rates. By comparison, the results of both algorithms are superior to multiple state-of-the-art methods. The overall framework proposed in this paper has superior performance and is capable of realizing high-quality and high-precision road segmentation and vehicle detection from UAV aerial images.

Abstract Background MCD (MYD88L265P/CD79Bmut) diffuse large B‐cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. Aims This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut. Materials and Methods Twenty‐three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) or rituximab + lenalidomide (R2). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R‐CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression‐free survival (PFS) of the two groups. Results The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R‐CHOP, and five elderly DLBCL patients were treated with BTKi + R2. Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1‐year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R‐CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R‐CHOP group had better PFS than patients in the control group. In the BTKi + R‐CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi‐type subgroups exhibited statistically significant differences in 1‐year PFS (p = 0.028). There were no significant differences in grade 3–4 haematological toxicity (p = 1) and grade 3–4 non‐haematological toxicity (p = 0.49) between the BTKi + R‐CHOP and R‐CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1‐year PFS rate was 80%. The incidences of grade 3–4 haematologic toxicity and non‐haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. Discussion The efficacy of BTKi combined with R‐CHOP was similar to previous reports, which was significantly better than R‐CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R‐CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non‐GCB, DEL or high‐IPI‐score DLBCL patients with MYD88mut and/or CD79Bmut. In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R‐miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. Conclusion This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real‐world clinical data.

BackgroundThe persistence of inflammatory stimulus has a tight relationship with the development of age-related diseases, ultimately resulting in a gradual escalation in the prevalence of tumors, but this phenomenon is rare in young cancer patients. Breast cancer arising in young women is characterized by larger tumor diameters and more aggressive subtypes, so neoadjuvant chemotherapy (NACT) can be especially appropriate for this population. Immune inflammatory biomarkers have been reportedly linked to the prognosis of some malignant tumor types, with varying results. In this study, we investigated the possible predictive value of blood-based markers in young breast cancer patients undergoing NACT, in addition to the association between the clinicopathological features and prognosis.MethodsFrom December 2011 to October 2018, a total of 215 young breast cancer patients referred to Harbin Medical University Cancer Hospital received NACT and surgery were registered in this retrospective study. The pretreatment complete blood counts were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV).ResultsNLR, PLR, MLR, and PIV optimal cut-off values were 1.55, 130.66, 0.24, and 243.19, as determined by receiver operating characteristic analysis. Multivariate analysis revealed that PIV, HR status, HER-2 status, and Ki-67 index were all independent predictive factors for pathological complete response. Subgroup analysis revealed that young breast cancer patients in the population characterized by low PIV and HR negative group were more likely to get pCR (P=0.001). The five-year overall survival (OS) rate was 87.9%, and Cox regression models identified PIV as independently related to OS.ConclusionIn the present study, the pretreatment PIV was found to be a useful prognostic indicator for pCR and long-term survival in young breast cancer patients undergoing NACT. High immune and inflammation levels, MLR and PIV were connected to poor clinical prognosis in young breast cancer patients. PIV is a promising biomarker to guide strategic decisions in treating young breast cancer.

A completely new poly(carbonate-ester) macrodiol (PPCP-mDL), derived from direct copolymerization of carbon dioxide (CO2), propylene oxide (PO), phthalic anhydride (PA) and 1, 4-butanediol (BDO) catalyzed by metal-free triethylborine (TEB)/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) pairs has been developed. The molecular weight of PPCP-mDL produced varying from 1.1–2.3 kg mol−1 can be easily controlled through the regulation of reaction conditions. For the formulation of non-toxic, phthalate-free flexible PVC, novel and biodegradable ec-PPCP-mDL with high molecular weight may be obtained through end-capping the PPCP-mDL using benzoyl chloride. The ec-PPCP-mDL/PVC blends display better comprehensive plasticization performance than do comparable blends with commercial DEHP plasticizers. These blends exhibit high thermal stability, mechanical properies, plasticizer migration resistance and transmittance. The interaction between ec-PPCP-mDL and PVC has been characterized using FTIR spectroscopy. A possible mode of plasticization has been suggested. The rich ester groups in the structure of ec-PPCP-mDLs interact well with PVC via hydrogen bonding, resulting in excellent compatiblity with PVC. Overall, the novel ec-PPCP-mDL material, respects an attractive alternative to plasticizers as a green, non-toxic, biodegradable, partially sustainable for the preparation of flexible PVC formulations.