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Eutrophication occurs frequently in urban water bodies, and rapid measurement of phosphorus (P) is needed for water quality control, since P has been one of the limiting factors. In this study, approximately 400 water samples were collected from typical urban water bodies in Nanjing city, and Fourier transform infrared attenuated total reflectance spectroscopy (FTIR-ATR) was applied for rapid P determination. Both silicon ATR (Si-ATR) and ZnSe-ATR were employed in the recording of FTIR-ATR spectra, and different algorithms, including partial least squares regression (PLSR), support vector machines for regression (SVRs), extreme learning machines (ELMs), and self-adaptive partial least squares model (SA–PLS), were applied in the analysis of spectra data. The results showed that the water quality varied significantly for different water bodies in different seasons, and both Si-ATR and ZnSe-ATR could achieve good P prediction. The PLSR and SVR models showed poor P prediction effects while the ELM model was excellent, and the SA-PLS model was the best one. For the SA-PLS model, the prediction accuracy of Si-ATR (Rv2 = 0.973, RMSEV = 0.015 mg L−1, RPDV = 6.05) was slightly better than that of ZnSe-ATR (Rv2 = 0.942, RMSEV = 0.011 mg L−1, RPDV = 4.13). Therefore, the FTIR-ATR technology coupled with the SA-PLS model achieved rapid P determination in urban water, providing an effective option for water quality monitoring.

This paper investigates the formation control problem of multi-unmanned aerial vehicle (UAV) systems with multi-operating modes. While mode switching enhances the flexibility of multi-UAV systems, it also introduces dynamic model switching behaviors in UAVs. Moreover, obtaining an accurate dynamic model for a multi-UAV system is challenging in practice. In addition, communication link failures and time-varying unknown disturbances are inevitable in multi-UAV systems. Hence, to overcome the adverse effects of the above challenges, a hybrid iterative learning formation control strategy is proposed in this paper. The proposed controller does not rely on precise modeling and exhibits its learning ability by utilizing historical input–output data to update the current control input. Furthermore, two convergence theorems are proven to guarantee the convergence of state, disturbance estimation, and formation tracking errors. Finally, three simulation examples are conducted for a multi-UAV system consisting of four quadrotor UAVs under multi-operating modes, switching topologies, and external disturbances. The results of the simulations show the strategy’s effectiveness and superiority in achieving the desired formation control objectives.

With the rapid development of optical communication and quantum information, the demand for efficient and broadband nonlinear frequency conversion has increased. At present, most single-frequency conversion processes in lithium niobate on insulator (LNOI) waveguides suffer from lateral leakage without proper design, leading to an additional increase in propagation loss. Achieving broadband frequency conversion also encounters this problem in that there are no relevant works that have solved this yet. In this paper, we theoretically propose an efficient and flat broadband second harmonic generation (SHG) in silicon nitride loaded apodized chirped periodically poled LNOI waveguides. By using a bound states in the continuum (BICs) mechanism to reduce the propagation loss and utilizing the characteristic that the BICs are insensitive to wavelength, an ultra-low-loss wave band of 80 nm is realized. Then, by employing an apodized chirped design, a flat broadband SHG is achieved. The normalized conversion efficiency (NCE) is approximately 222%W−1cm−2, and the bandwidth is about 100 nm. Moreover, the presented waveguides are simple and can be fabricated without direct etching of lithium niobate, exhibiting excellent fabrication tolerance. Our work may open a new avenue for exploring low-loss and flat broadband nonlinear frequency conversion on various on-chip integrated photonic platforms.

When constructing a multiple automated guided vehicle (multi-AGV) system, it is essential to calculate the potential values of the system’s feature parameters. This article presents two time-cost calculators and an improved simulation platform for scientifically estimating the cost of constructing a multi-AGV system. By inputting the parameters of the number of automated guided vehicles (AGVs), the velocity of the AGV, the number of tasks, scheduling interval and path length, the designed calculator can output the system’s time expense when all tasks are completed. The designed simulation platform can display a specific multi-AGV system’s time cost and how the entire progress works in a visual interface. An advanced scheduling method based on handover mode and A* algorithm is used to solve task scheduling problems in a multi-AGV system. The overall performance of the newly integrated scheduling system is compared with other scheduling systems to validate its superiority and shortcomings in different corresponding work scenarios. The final results present a robust solution to improve a multi-AGV system’s effectiveness.

IntroductionThis study aimed to explore the transcriptomic profile of premature ovarian insufficiency (POI) by investigating alterations in gene expression.MethodsA total of sixty-one women, comprising 31 individuals with POI in the POI group and 30 healthy women in the control group (HC group), aged between 24 and 40 years, were recruited for this study. The transcriptomic profiles of peripheral blood samples from all study subjects were analyzed using RNA-sequencing.ResultsThe results revealed 39 differentially expressed genes in individuals with POI compared to healthy controls, with 10 upregulated and 29 downregulated genes. Correlation analysis highlighted the relationship between the expression of SLC25A39, CNIH3, and PDZK1IP1 and hormone levels. Additionally, an effective classification model was developed using SLC25A39, CNIH3, PDZK1IP1, SHISA4, and LOC389834. Functional enrichment analysis demonstrated the involvement of these differentially expressed genes in the “haptoglobin-hemoglobin complex,” while KEGG pathway analysis indicated their participation in the “Proteoglycans in cancer” pathway.ConclusionThe identified genes could play a crucial role in characterizing the genetic foundation of POI, potentially serving as valuable biomarkers for enhancing disease classification accuracy.

Introduction Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found.Methods/design The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35–45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases.Ethics and dissemination The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300072472).

PurposeThis study was based on the Global Burden of Disease (GBD) database and aimed to analyze the trend of disease burden for complete edentulism in Chinese adults between 1990 and 2030, and to provide valuable information for the development of more effective management and preventive measures.MethodsData on Chinese adults with complete edentulism from 1990 to 2019 was analyzed using GHDx data. Descriptive analyses were used to analyze changes in the prevalence and burden of complete edentulism, gender and age distribution between 1990 and 2019. In addition, we used an autoregressive integrated moving average (ARIMA) model to predict the trend of disease burden for Chinese adults with complete edentulism between 2020 and 2030.ResultsThe incidence, prevalence, and rate of YLDs in adults with complete edentulism in China showed an increasing trend from 1990 to 2019. In 2019, the incidence was 251.20 per 100,000, the prevalence was 4512.78 per 100,000, and the YLDs were 123.44 per 100,000, marking increases of 20.58, 94.18, and 93.12% from 1990. Males experienced a higher increase than females. However, the standardized rates decreased over the same period. The ARIMA model predicts a subsequent upward and then downward trend for all indicators between 2019 and 2030, except for the standardized incidence rate which remained essentially unchanged. Specifically, the incidence is predicted to decrease from 388.93 to 314.40 per 100,000, prevalence from 4512.78 to 3049.70 per 100,000, and YLDs from 123.44 to 103.44 per 100,000. The standardized prevalence and YLDs rates are also expected to decrease.ConclusionThe burden of complete edentulism in China is projected to show an increasing trend from 2020 to 2022 and a decreasing trend from 2023 to 2030. Despite the decline in the burden of disease associated with complete edentulism in China, many problems remain to be solved.

Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 μM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development.

Breast cancer has become the most prevalent malignancy worldwide; however, therapeutic efficacy is far from satisfactory. To alleviate the burden of this disease, it is imperative to discover novel mechanisms and treatment strategies. Protein phosphatase 2 A (PP2A) comprises a family of mammalian serine/threonine phosphatases that regulate many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathologies, and plays a pivotal role in the initiation and progression of tumours. The role of PP2A as a tumour suppressor has been extensively studied, and its regulation can serve as a target for anticancer therapy. Recent studies have shown that PP2A is a tumour promotor. PP2A-mediated anticancer therapy may involve two opposing mechanisms: activation and inhibition. In general, the contradictory roles of PP2A should not be overlooked, and more work is needed to determine the molecular mechanism by which PP2A affects in tumours. In this review, the literature on the role of PP2A in tumours, especially in breast cancer, was analysed. This review describes relevant targets of breast cancer, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may lead to effective therapeutic strategies or influence drug development in breast cancer.

Multimodal emotion recognition techniques are increasingly essential for assessing mental states. Image-based methods, however, tend to focus predominantly on overt visual cues and often overlook subtler mental state changes. Psychophysiological research has demonstrated that heart rate (HR) and skin temperature are effective in detecting autonomic nervous system (ANS) activities, thereby revealing these subtle changes. However, traditional HR tools are generally more costly and less portable, while skin temperature analysis usually necessitates extensive manual processing. Advances in remote photoplethysmography (r-PPG) and automatic thermal region of interest (ROI) detection algorithms have been developed to address these issues, yet their accuracy in practical applications remains limited. This study aims to bridge this gap by integrating r-PPG with thermal imaging to enhance prediction performance. Ninety participants completed a 20-min questionnaire to induce cognitive stress, followed by watching a film aimed at eliciting moral elevation. The results demonstrate that the combination of r-PPG and thermal imaging effectively detects emotional shifts. Using r-PPG alone, the prediction accuracy was 77% for cognitive stress and 61% for moral elevation, as determined by a support vector machine (SVM). Thermal imaging alone achieved 79% accuracy for cognitive stress and 78% for moral elevation, utilizing a random forest (RF) algorithm. An early fusion strategy of these modalities significantly improved accuracies, achieving 87% for cognitive stress and 83% for moral elevation using RF. Further analysis, which utilized statistical metrics and explainable machine learning methods including SHapley Additive exPlanations (SHAP), highlighted key features and clarified the relationship between cardiac responses and facial temperature variations. Notably, it was observed that cardiovascular features derived from r-PPG models had a more pronounced influence in data fusion, despite thermal imaging’s higher predictive accuracy in unimodal analysis.

Abstract Background The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis. Results A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%). Conclusions This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.

Abstract Background and purpose To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value

Abstract Background This study sought to compare the benefits and safety of agents including Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors as second-line treatments for these patients by conducting a comprehensive systematic review and network meta-analysis. Methods The Medline, Embase and Cochrane Library databases were searched for randomized trials comparing CDK4/6 inhibitors, PI3K/mTOR inhibitors, or HDAC inhibitors vs. placebo with the addition of exemestane or fulvestrant as second-line treatments in patients with HR + advanced breast cancer up to December 16, 2021. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), clinical benefit rate (CBR), and grade 3–4 adverse drug events (ADEs). The present study was conducted according to the Cochrane Collaboration and PRISMA statements. The overall effect was pooled using the random effects model. Results Seventeen studies with a total of 9,100 participants were included in the current study. Compared with placebo plus fulvestrant, PFS was significantly improved by CDK4/6 inhibitor plus fulvestrant, mTOR inhibitor plus fulvestrant, mTOR inhibitor plus exemestane, and PI3K inhibitor plus fulvestrant, but not HDAC inhibitor plus exemestane. While mTOR inhibitor plus exemestane was the best regimen (SUCRA value 89.5%), the mTOR inhibitor plus exemestane regimen induced more severe adverse events (SAEs) than the HDAC inhibitor plus exemestane regimen [OR, 95% CI: 2.40 (1.40–4.10)]. Conclusion mTOR inhibitor and CDK4/6 inhibitor-based regimens demonstrated superior clinical efficacy and comparable safety profiles as second-line treatment in patients with HR-positive, HER2-negative advanced breast cancer.

Abstract Background This single‐arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in women with HER2‐negative metastatic breast cancer (MBC) in China. Methods The mNC regimen was administered to the enrolled cases, including oral vinorelbine (VNR) 40 mg three times weekly (on days 1, 3 and 5 every week) and capecitabine (CAP) 500 mg three times a day, until disease progression or intolerable toxicity. The primary endpoint was the 1‐year progression‐free survival (PFS) rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and treatment‐related adverse events (TRAEs). Stratified factors included treatment lines and hormone receptor (HR) status. Results Between June 2018 and March 2023, 29 patients were enrolled into the study. The median follow‐up time was 25.4 months (range, 2.0–53.8). In the entire group, the 1‐year PFS rate was 54.1%. ORR, DCR and CBR were 31.0%, 96.6% and 62.1%, respectively. The mPFS was 12.5 months (range, 1.1–28.1). Subgroup analysis revealed that ORRs were 29.4% and 33.3% in first‐ and ≥second‐line chemotherapy, respectively. ORRs were 29.2% (7/24) and 40.0% (2/5) for HR‐positive MBC and metastatic triple‐negative breast cancer (mTNBC), respectively. Grade 3/4 TRAEs were neutropenia (10.3%) and nausea/vomiting (6.9%). Conclusions The dual oral mNC regimen showed very good safety features and improved compliance without loss of efficacy in both first‐ and second‐line treatments. The regimen also reached an excellent ORR in the mTNBC subgroup.

This paper proposes an enhanced multi-strategy sparrow search algorithm to optimize the trajectory of a six-axis industrial robot, addressing issues of low efficiency and high vibration impact on joints during operation. Initially, the improved D-H parametric method is employed to establish both forward and inverse kinematic models of the robot. Subsequently, a 3-5-3 mixed polynomial interpolation trajectory planning approach is applied to the robot. Building upon the conventional sparrow algorithm, a two-dimensional Logistic chaotic system initializes the population. Additionally, a Levy flight strategy and nonlinear adaptive weighting are introduced to refine the discoverer position update operator, while an inverse learning strategy enhances the vigilante position update operator. These modifications boost both the local and global search capabilities of the algorithm. The improved sparrow algorithm, based on 3-5-3 hybrid polynomial trajectory planning, is then used for the time-optimal trajectory planning of the robot. This is compared with traditional sparrow search algorithm and particle swarm algorithm optimization results. The findings indicate that the proposed enhanced sparrow search algorithm outperforms both the standard sparrow algorithm and the particle swarm algorithm in terms of convergence speed and accuracy for robot trajectory optimization. This can lead to the increased work efficiency and performance of the robot.

Cadmium is the main heavy metal contaminant of food in the world. The extent of cadmium pollution in peanut in China remains unclear. To determine the cadmium pollution level in peanut, samples from the main producing regions in China were assessed. The findings revealed that the cadmium pollution level in Chinese peanuts was relatively low. Moreover, the Aflatoxin Rhizobia Couple B. amyloliquefaciens, B. laterosporu, B. mucilaginosus, E. ludwiggi (ARC-BBBE) microbial inoculants on cadmium contamination in peanut were evaluated. The fertilization methods were categorized into conventional fertilization and conventional fertilization supplemented with 60 kg/hectare of microbial inoculant ARC-BBBE as the base fertilizer. The cadmium contents in the soil and peanut plant parts were detected and analyzed. The results demonstrated that the microbial inoculant ARC-BBBE significantly reduced the total cadmium content in peanut, as well as the available cadmium and exchangeable cadmium in soil. Furthermore, the pH and urease and alkaline phosphatase activities in soil were significantly enhanced, suggesting that the microbial inoculant ARC-BBBE decreased cadmium content in soil and reduced the cadmium uptake by plants through a combination of the action of the bacteria itself and the secretion of extracellular substances. This ultimately achieves the goal of reducing the cadmium content in peanut seeds.

In this note we proved that each nonlinear generalized semi-Jordan triple derivable mapping on completely distributive commutative subspace lattice algebras is an additive derivation.

Abstract Thanks to the significantly higher energy density compared with universal commercialized Li‐ion batteries, lithium–sulfur (Li–S) batteries are being investigated for use in prospective energy storage devices. However, the inadequate electrochemical kinetics of reactants and intermediates hinder commercial utilization. This limitation results in substantial capacity degradation and short battery lifespans, thereby impeding the battery's power export. Meanwhile, the capacity attenuation induced by the undesirable shuttle effect further hinders their industrialization. Considerable effort has been invested in developing electrocatalysts to fix lithium polysulfides and boost their conversion effectively. In the conventional process, the planar electrodes are prepared by slurry‐casting, which limits the electron and ion transfer paths, especially when the thickness of the electrodes is relatively large. Compared with traditional manufacturing methods, direct ink writing (DIW) technology offers unique advantages in both geometry shaping and rapid prototyping, and even complex three‐dimensional structures with high sulfur loading. Hence, this review presents a detailed description of the current developments in terms of Li–S batteries in DIW of metal‐based electrocatalysts. A thorough exploration of the behavior chemistry of electrocatalysis is provided, and the adhibition of metal‐based catalysts used for Li–S batteries is summarized from the aspect of material usage and performance enhancement. Then, the working principle of DIW technology and the requirements of used inks are presented, with a detailed focus on the latest advancements in DIW of metal‐based catalysts in Li–S battery systems. Their challenges and prospects are discussed to guide their future development.

Abstract Background Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastasis (BrM) and a poor prognosis. As the most lethal form of breast cancer, BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis (BCBrM), but the underlying mechanisms are far from being fully elucidated. Methods Through analysis of BCBrM transcriptome data from mice and patients, and immunohistochemical validation on patient tissues, we identified and verified the specific down-regulation of retinoic acid receptor responder 2 (RARRES2), a multifunctional adipokine and chemokine, in BrM of TNBC. We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies. Key signaling pathway components were evaluated using multi-omics approaches. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2. Results We found that down-regulation of RARRES2 is specifically associated with BCBrM, and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue (PTEN)-mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment. Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM. RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Abstract Purpose To establish an early clinical diagnosis model based on the retinal vascular features associated with POI, supplying a non-invasive way for accurately and early predicted the risk of POI. Methods A total of 78 women with spontaneous POI and 48 healthy women were recruited from the Affiliated Shenzhen Maternity & Child Healthcare Hospital in the study. Retinal characteristics were analyzed using an automated retinal image analysis system. Binary logistic regression was used to identify POI cases and develop predictive models. Results Compared to the normal group, the POI group had larger central retinal artery equivalent (CRAE) (P = 0.006), central retinal vein equivalent (CRVE) (P = 0.001), index of venules asymmetry (Vasym) (P = 0.000); larger bifurcation angles of arterioles (Aangle) (P = 0.001), bifurcation coefficient of venule (BCV) (P = 0.001) and more obvious arteriovenous nipping (Nipping) (P = 0.005), but lower arteriole-to-venule ratio (AVR) (P = 0.012). In the POI group, the odds ratio (OR) of Vasym was 6.72e-32 (95% C.I. 4.62e-49–9.79e-15, P = 0.000), the OR of BCV was 5.66e-20 (95% C.I. 1.93e-34–.0000, P = 5.66e-20) and the OR of Nipping was 6.65e-06 (95% C.I. 6.33e-10–.0698, P = 0.012). Moreover, the area under the ROC curve for the binary logistic regression with retinal characteristics was 0.8582, and the fitting degree of regression models was 60.48% (Prob > chi-square = 0.6048). Conclusion This study demonstrated that retinal image analysis can provide useful information for POI identification and certain characteristics may help with early clinical diagnosis of POI.

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Background: This study was conducted to evaluate the efficacy and safety of docetaxel/S-1 (TS) compared with docetaxel/capecitabine (TX) as a first-line treatment for advanced breast cancer. Methods: Patients with advanced metastatic breast cancer were randomly divided into the TS group (n = 54) and the TX group (n = 57) for first-line chemotherapy from August 2015 to April 2019 (ClinicalTrials.org registration no. NCT02947061). Following the completion of combination therapy, patients without progression received S-1 or capecitabine maintenance treatment. The primary end point was progression-free survival (PFS). Results: Among 111 enrolled patients, the median PFS did not differ significantly between the TS group and the TX group (TS vs. TX, 9.0 vs. 7.4 months, P = 0.365, 95% confidence interval [CI]: 0.50–1.11, hazard ratio [HR]: 0.75). There was also no statistically significant difference in median overall survival (OS) between the two groups (TS vs. TX, 40.2 vs. 41.3 months, P = 0.976). In addition, visceral metastasis and metastasis sites, such as the liver or lung, did not lead to a significant effect on PFS and OS. The two regimens showed no significant difference in adverse events, except hand-foot syndrome, which predominated in the TX group (38.6% vs. 7.4%, P = 0.001), and diarrhea (24.1% vs. 3.6%, P = 0.003) and elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels (14.8% vs. 3.5%, P = 0.049), which were more frequent in the TS group. Conclusions: The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer. The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen, representing an effective alternative option to the TX regimen. Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.

Abstract Background Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single‐cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype‐associated subpopulations is challenging. Results Here, we applied Scissor (single‐cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC‐deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer‐associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC‐deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK‐STATs signaling. FABP5+ macrophages show low antigen‐presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T‐cell immune infiltration through cell interaction in breast tumor microenvironment. Conclusion Taken together, our study reveals survival‐associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.

Abstract Aims Inflammatory biomarkers, including CRP, the neutrophil‐to‐lymphocyte ratio (NLR), and the neutrophil‐to‐eosinophil ratio (NER), may predict outcomes in cancer. However, their value in immune checkpoint inhibitor (ICI) therapy‐associated cardiotoxicity remains elusive. We aimed to characterize the relationship of inflammatory markers with severity of ICI‐related cardiotoxicities (iRCs) and prognosis among patients with iRCs. Methods Patients who were diagnosed with iRCs between January 2019 and December 2021 were retrospectively enrolled and were dichotomized based on iRC severity into low‐grade (grade 1–2) vs. high‐grade (grade 3–4) groups. Results Forty‐seven patients were included. The median time‐to‐event from first ICI infusion to onset of iRCs was 35 days (IQR: 19.0–65.5 days). When compared with respective baseline values, cardiac biomarkers and inflammatory markers were significantly elevated at onset of iRCs. Compared with low‐grade iRCs, NER at iRC onset was significantly increased among patients with high‐grade iRCs (Group × Time, P

Abstract Background Breast cancer (BC) is the most common malignancy affecting women. It is vital to explore sensitive biological markers to diagnose and treat BC patients. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in breast tumor progression. Nonetheless, whether lncRNA prostate cancer‐associated transcript 19 (PCAT19) impacts BC development remains unknown. Methods We performed various bioinformatic analyses, including machine learning models to identify critical regulatory lncRNAs affecting prognosis in BC. The in situ hybridization (ISH) assay was carried out to confirm the expression levels of lncRNA PCAT19 in tissue specimens. MTT assay, wound healing assay, and transwell assay were performed to investigate PCAT19's impact on proliferation, migration, and invasion of BC cells. Mouse xenografts were used to examine the proliferation‐inhibiting function of PCAT19 in vivo. Results Among the prognosis‐associated lncRNAs, PCAT19 predicted a favorable prognosis in BC. Patients with high expression levels of PCAT19 had a lower clinical stage and less lymph node metastasis. The PCAT19‐related genes were enriched in signaling pathways involved in tumor development, indicating PCAT19 was an essential regulator of BC. Using the ISH assay, we confirmed the expression level of lncRNA PCAT19 in human BC tissues was lower than normal breast tissues. Moreover, the knockdown of PCAT19 further confirmed its inhibiting ability in BC cell proliferation. Correspondingly, overexpressing PCAT19 reduced tumor size in mouse xenografts. Conclusions Our study demonstrated that lncRNA PCAT19 suppressed the development of BC. PCAT19 might be a promising prognostic biomarker, which provides new insights into risk stratification for BC patients.

Abstract Background Disease stage at diagnosis and molecular subtypes are the main determinants of breast cancer treatment strategies and prognosis. We aimed at examining the disparities and factors associated with the stage at diagnosis among the molecular subtypes in breast cancer patients in China. Methods We identified patients with first primary breast cancer diagnosed between January 1, 2016, and December 31, 2017, from 23 hospitals in 12 provinces in China. We analyzed the proportion of non‐early‐stage (stages II–IV) breast cancer cases based on the family history of breast cancer, body mass index (BMI), insurance status, and molecular subtypes. Multivariable analyses were used to estimate the factors associated with non‐early‐stage diagnosis among the molecular subtypes. We further compared these estimates with that in the United States using the Surveillance, Epidemiology, and End Results database. Results A total of 9398 Chinese were identified with first primary invasive breast cancer. Of the 8767 patients with known stages, the human epidermal growth factor receptor 2 (HER2)‐enriched subtype had the highest proportion of stages II–IV (76.6%) patients, followed by triple‐negative breast cancer (73.2%), luminal B (69.9%), and luminal A (62.3%). The percentage of non‐early‐stage patients was higher in women with overweight or obesity than in those with a body mass index (BMI)

The world’s transportation system is overburdened by ever-growing travel demand, which brings mobility, safety, and pollution problems. To combat these issues and make better use of existing road capacity on urban arterials, public transit buses are designed to carry more people in fewer vehicles. However, transit buses travel slowly and make frequent intermittent stops, resulting in unreliable travel times and inconvenient riding experiences; this hinders people from choosing to travel on public transit buses. However, a research gap exists in using connected and automated vehicle (CAV) technologies specifically for transit bus operation optimization. To bridge this gap, the present study extended CAV applications to transit bus operation and developed a transit bus control method based on cooperative adaptive cruise control (CACC). The proposed model first optimized bus segment speeds to minimize schedule deviations and fuel consumption. Then, a CACC algorithm was integrated with optimal segment speed. The proposed control method was implemented through micro-simulations of an actual corridor in Jinan, Shandong, China. The evaluation results indicate that the proposed control method reduced the total arrival deviation up to 65.1% and total fuel consumption up to 6.8%. The study adapts CAV technologies to transit bus operation. The findings in this study validate CAV applications in transit bus operation.

Low back pain caused by disc herniation and spinal stenosis imposes an enormous medical burden on society due to its high prevalence and refractory nature. This is mainly due to the long-term inflammation and degradation of the extracellular matrix in the process of intervertebral disc degeneration (IVDD), which manifests as loss of water in the nucleus pulposus (NP) and the formation of fibrous disc fissures. Biomaterial repair strategies involving hydrogels play an important role in the treatment of intervertebral disc degeneration. Excellent biocompatibility, tunable mechanical properties, easy modification, injectability, and the ability to encapsulate drugs, cells, genes, etc. make hydrogels good candidates as scaffolds and cell/drug carriers for treating NP degeneration and other aspects of IVDD. This review first briefly describes the anatomy, pathology, and current treatments of IVDD, and then introduces different types of hydrogels and addresses “smart hydrogels”. Finally, we discuss the feasibility and prospects of using hydrogels to treat IVDD.

ABSTRACTBackground Despite poor oral hygiene, the Baiku Yao (BKY) ethnic group in China presents a low prevalence of dental caries, which may be related to genetic susceptibility. Due to strict intra-ethnic marriage rule, this ethnic has an advantage in studying the interaction between genetic factors and other regulatory factors related to dental caries.Methods Peripheral blood from a caries-free adult male was used for whole genome sequencing, and the BKY assembled genome was compared to the Han Chinese genome. Oral saliva samples were collected from 51 subjects for metabolomic and metagenomic analysis. Multiomics data were integrated for combined analysis using bioinformatics approaches.Results Comparative genomic analysis revealed the presence of structural variations in several genes associated with dental caries. Metabolomic and metagenomic sequencing demonstrated the caries-free group had significantly higher concentration of antimicrobials and higher abundance of core oral health-related microbiota. The functional analysis indicated that cationic antimicrobial peptide resistance and the lipopolysaccharide biosynthesis pathway were enriched in the caries-free group.Conclusions Our study provided new insights into the specific regulatory mechanisms that contribute to the low prevalence of dental caries in the specific population and may provide new evidence for the genetic diagnosis and control of dental caries.

Purpose: To analyze the safety and efficacy of orally administered metronomic capecitabine plus pyrotinib in HER2 positive metastatic breast cancer (MBC) patients, we conducted a prospective phase II study with a single-arm design. Methods: HER2 positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety. Results: The study included 50 patients with MBC that was HER2-positive, while 1 patient was excluded due to nonstandard medication. The median PFS and OS was 11.9 months (95%CI 8.8–14.6) and 29.3 months (95%CI 24.4–34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse events included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15(30.6%) patients, including hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). 1 grade 4 adverse event of diarrhea (2.0%) was observed. Conclusion: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2 positive metastatic breast cancer patients.

Objective: Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro. This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2−) recurrent or metastatic breast cancer. Methods: Patients were intramuscularly administered fulvestrant 500 mg (day 1 per cycle for 28 days) and oral vinorelbine (60 mg/m2 on days 1, 8, and 15 of each cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, objective response rate, disease control rate, duration of response, and safety. Results: A total of 38 patients with HR+/HER2− advanced breast cancer included in the study were followed up for a median time of 25.1 months. The overall median PFS was 9.86 months [95% confidence interval (CI) 7.2–23.13], and the median PFS of the first-line and the second-line treatment population was 20.73 months (95% CI 9.82 to NR) and 4.27 months (95% CI 3.68 to NR), respectively. Most adverse events reported were of grade 1/2, and none were of grade 4/5. Conclusions: This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2− recurrent and metastatic breast cancer. The combination chemo-endocrine therapy was efficacious, safe, and promising for patients with HR+/HER2− advanced breast cancer.

Abstract To investigate the correlation between cluster of differentiation-44 (CD44) expression and immunotherapy response and identify its possible predictive value in pan-cancer. Datasets of 33 cancer types from The Cancer Genome Atlas (TCGA) database were applied to investigate the relationship of CD44 expression with prognosis, tumor mutational burden (TMB), and microsatellite instability (MSI), and determine its potential prognostic value in pan-cancer. Patients were split into high-risk and low-risk cancer groups based on the survival outcomes of various cancer types. Additionally, the underlying mechanisms of CD44 in the tumor microenvironment (TME) were analyzed using ESTIMATE and CIBERSORT algorithms and Gene Set Enrichment Analysis (GSEA). Subsequently, the biological role of CD44 at single-cell level was investigated using CancerSEA database. Variable expression levels of CD44 between tumor and adjacent normal tissues were identified in pan-cancer datasets, further survival analysis revealed that CD44 expression was associated with multiple clinical annotations and survival indicators. Besides, the expression of CD44 was significantly associated with TMB and MSI in 10 types and 6 types of cancer, respectively, indicating it could be exploited as a potential biomarker predicting immunotherapy outcomes. Meanwhile, CD44 could influence several crucial immune cell-related pathways. and the results revealed by CancerSEA database denoted the correlation of CD44 with malignant phenotype and functional states, further indicating it can serve as a potential therapeutic target in cancer management. Our study demonstrated that CD44 shows great promise as a prognostic biomarker in numerous cancers, which will assist in developing new strategies in cancer management.

Abstract Background The mutual compensatory relationship between the upper cervical sagittal alignment and the lower cervical sagittal alignment has been repeatedly reported. However, the evaluation of the upper cervical sagittal parameters are varied in previous studies. This retrospective study was performed to compare three methods for measuring the upper cervical sagittal parameters. Methods A total of 263 individuals with standing neutral lateral cervical radiographs were included in this study. The Frankfort horizontal line (FHL), foramen magnum line (FML), and McGregor line (ML) were separately used as the reference lines for measuring the C0-1 angle and C0-2 angle. Intraclass correlation (ICC) values were used to compare the consistency and repeatability of the three methods. Pearson’s correlation analysis was used to analyze the correlation between the sagittal parameters of the upper and lower cervical spine. Results The interobserver and intraobserver ICC values obtained from using the ML to measure the C0-1 angle and C0-2 angle were both higher than those obtained from using the FML or FHL. The C0-1 angle and C0-2 angle measured by the three methods were negatively correlated with the C2-7 angle. The upper sagittal parameters measured by the FHL were the most correlated with the C2-7 angle. The correlation between the C0-1 angle measured by the three methods and the C0-2 angle measured with the FHL or ML and the C2-7 angle increased with aging. Conclusion Use of the ML to measure the C0-1 angle and C0-2 angle has higher reliability. Use of the FHL to measure the sagittal alignment of the upper cervical spine is more suitable for evaluating the compensation mechanism between the upper and the lower cervical spine.

The reservoir is an important component of hydraulic projects for supplying water to the city. For guaranteeing reservoir safe operation, stepped spillways are often used to discharge the flood from the reservoir. But under large unit discharges, cavitation erosion and low energy dissipation may occur on stepped spillways, which possibly leads to the hydraulic structures being instable and the reservoir outwork for water supply. Herein, an orifice plate is introduced as a pre-aeration device for the stepped spillways to avoid cavitation damage. To detail the effect of orifice plate on the flow over the stepped spillways, experiments were conducted. The results demonstrate that the orifice plate contracted the flow into a jet. Large amounts of air were entrained, and cavitation damage could be avoided according to the air concentration distributions along the stepped spillways. The orifice plate also significantly increased the energy dissipation of stepped spillways. Further, flow depth before the orifice plate increased because of flow block, and was emphatically discussed for providing a calculation formula to estimate the jet trajectory. HIGHLIGHTS The orifice plate generates a jet to entrain air, which can avoid cavitation damage for stepped spillways with large unit discharges.; The orifice plate increases the energy dissipation of the stepped spillway.; The relationship of take-off flow depth and hydraulic as well as structure parameters of the orifice plate are revealed.; This paper presents the formula of jet trajectory based on the corrected take-off flow depth.;

To reveal the characteristic chemicals of walnuts from different origins, we analyzed fatty acid composition, tocopherols, phytosterols and total phenolic content (TPC) of walnuts from three main producing regions in China. The results showed that walnuts were rich in polyunsaturated fatty acids, and the ratio of ω-6 to ω-3 fatty acids was close to the recommendation of Chinese Nutrition Society. Moreover, walnuts contain high contents of tocopherols (331.20–414.71 ​mg/kg), phytosterols (97.17–110.35 ​mg/100 ​g) and phenols (38.51–48.08 ​mg GAE/kg). Significant chemical differences exist among walnuts from three production regions. The highest content of polyunsaturated fatty acids was found in walnuts from the northern China, the highest content of tocopherols in walnuts from southwest China, and the highest contents of phytosterol and TPC in walnuts from northwest China. However, there was no significant difference in the tocopherol, phytosterol and TPC content of walnuts between the Northern China and Northwest China. The above results provide important references for manufacturers and consumers to select suitable walnut scientifically and reasonably.

Abstract Background Breast cancer (BC) metastasis is the leading cause of poor prognosis and therapeutic failure. However, the mechanisms underlying cancer metastasis are far from clear. Methods We screened candidate genes related to metastasis through genome-wide CRISPR screening and high-throughput sequencing of patients with metastatic BC, followed by a panel of metastatic model assays. The effects of tetratricopeptide repeat domain 17 (TTC17) on migration, invasion, and colony formation ability together with the responses to anticancer drugs were investigated in vitro and in vivo. The mechanism mediated by TTC17 was determined by RNA sequencing, Western blotting, immunohistochemistry, and immunofluorescence. The clinical significance of TTC17 was evaluated using BC tissue samples combined with clinicopathological data. Results We identified the loss of TTC17 as a metastasis driver in BC, and its expression was negatively correlated with malignancy and positively correlated with patient prognosis. TTC17 loss in BC cells promoted their migration, invasion, and colony formation capacity in vitro and lung metastasis in vivo. Conversely, overexpressing TTC17 suppressed these aggressive phenotypes. Mechanistically, TTC17 knockdown in BC cells resulted in the activation of the RAP1/CDC42 pathway along with a disordered cytoskeleton in BC cells, and pharmacological blockade of CDC42 abolished the potentiation of motility and invasiveness caused by TTC17 silencing. Research on BC specimens demonstrated reduced TTC17 and increased CDC42 in metastatic tumors and lymph nodes, and low TTC17 expression was linked to more aggressive clinicopathologic characteristics. Through screening the anticancer drug library, the CDC42 inhibitor rapamycin and the microtubule-stabilizing drug paclitaxel showed stronger inhibition of TTC17-silenced BC cells, which was confirmed by more favorable efficacy in BC patients and tumor-bearing mice receiving rapamycin or paclitaxel in the TTC17Low arm. Conclusions TTC17 loss is a novel factor promoting BC metastasis, that enhances migration and invasion by activating RAP1/CDC42 signaling and sensitizes BC to rapamycin and paclitaxel, which may improve stratified treatment strategies under the concept of molecular phenotyping-based precision therapy of BC.

As important supplementary to major edible oils, comparative chemical advantages of minor edible oils decide their development and usage. In this study, chemical composition of 13 kinds of specific edible vegetable oils were investigated. The comparative advantages of chemical compositions of these edible oils were obtained as follows: (1) camellia, tiger nut and almond oil were rich in oleic acid, the contents of which accounted for 79.43%, 69.16% and 66.26%, respectively; (2) safflower oil contained the highest content of linoleic acid (76.69%), followed by grape seed (66.85%) and walnut oil (57.30%); (3) perilla seed, siritch, peony seed and herbaceous peony seed oil were rich in α-linolenic acid (59.61%, 43.74%, 40.83% and 30.84%, respectively); (4) the total phytosterol contents of these oils ranged from 91.46 mg/100 ​g (camellia oil) to 506.46 mg/100 ​g (siritch oil); and (5) The best source of tocopherols was sacha inchi oil (122.74 mg/100 ​g), followed by perilla seed oil (55.89 mg/100 ​g), peony seed oil (53.73 mg/100 ​g) and herbaceous peony seed oil (47.17 mg/100 ​g). The comparative advantages of these specific edible oils indicated that they possess the high potential nutritional values and health care functions.

The borehole heat exchanger (BHE) is a key component using shallow geothermal energy in ground source heat pump systems (GSHPS), and reasonable pipe spacing design has a great impact on the heat transfer performance and economy of the GSHPs. In most of real applications, the thermal disturbance radius of the maximum heat load per unit length (that is, the most unfavorable case) is often used as the design basis, and this makes it difficult to achieve the technical and economic optimization of the ground source heat pump system. This paper proposes a simple but more practical mathematical method to obtain the thermal disturbance radius of the borehole heat exchanger. The method first derives an analytical solution of the formation temperature distribution around the borehole under the boundary condition of periodic heat flow. On this basis, the actual dynamic building heating and cooling load is approximately expanded into a finite of sine and cosine periodic functions with the Fourier series. By superimposing the analytical solution corresponding to each periodic function obtained by Fourier series expansion of the original dynamic load, the variation of formation temperature distribution under the actual dynamic heating and cooling load conditions can be obtained.

Abstract Background Neonatal sepsis (NS), a life-threatening condition, is characterized by organ dysfunction and is the most common cause of neonatal death. However, the pathogenesis of NS is unclear and the clinical inflammatory markers currently used are not ideal for diagnosis of NS. Thus, exploring the link between immune responses in NS pathogenesis, elucidating the molecular mechanisms involved, and identifying potential therapeutic targets is of great significance in clinical practice. Herein, our study aimed to explore immune-related genes in NS and identify potential diagnostic biomarkers. Datasets for patients with NS and healthy controls were downloaded from the GEO database; GSE69686 and GSE25504 were used as the analysis and validation datasets, respectively. Differentially expressed genes (DEGs) were identified and Gene Set Enrichment Analysis (GSEA) was performed to determine their biological functions. Composition of immune cells was determined and immune-related genes (IRGs) between the two clusters were identified and their metabolic pathways were determined. Key genes with correlation coefficient > 0.5 and p

Abstract Objective The purpose of this study was to evaluate the feasibility of a novel technique named spinal joints release (SJR) and observe its efficacy in treating rigid post-traumatic thoracolumbar kyphosis (RPTK). Methods RPTK patients who were treated by SJR with facet resection, limited laminotomy, clearance of the intervertebral space, and release of the anterior longitudinal ligament through the intervertebral foramen and disc of injury segment from August 2015 to August 2021 were reviewed. Intervertebral space release, internal fixation segment, operation time, and intraoperative blood loss were recorded. The intraoperative, postoperative, and final follow-up complications were observed. An improvement in the VAS score and ODI index was observed. Spinal cord functional recovery was evaluated by American Spinal Injury Association Impairment Scale (AIS). Improvement of local kyphosis (Cobb angle) was evaluated by radiography. Results Forty-three patients were successfully treated by the SJR surgical technique. Open-wedge anterior intervertebral disc space was performed in 31 cases, and repeated release and dissection of the anterior longitudinal ligament and callus were performed in 12 cases. There was no lateral annulus fibrosis release in 11 cases, the anterior half release of lateral annulus fibrosis in 27 cases, and complete release in five cases. There were five cases of screw placement failure in one or two side pedicles of the injured vertebrae due to excessive resection of the facets and improper pre-bending of the rod. Sagittal displacement occurred in four cases at the released segment due to the complete release of bilateral lateral annulus fibrosus. Autologous granular bone + Cage was implanted in 32 cases, and autologous granular bone was implanted in 11 cases. There were no serious complications. The average operation time was 224 ± 31 min, and intraoperative blood loss was 450 ± 225 mL. All the patients were followed up with an average of 26 ± 8.5 months. The VAS scores and ODI index improved significantly at the final follow-up. All of the 17 patients with incomplete spinal cord injury achieved more than one grade of neurological recovery at the final follow-up. An 87% correction rate of kyphosis was achieved and maintained, with the Cobb angle decreasing from 27.7° preoperatively to 5.4° at the final follow-up. Conclusion Posterior SJR surgery for patients with RPTK has the advantages of less trauma and less blood loss, and kyphosis correction is satisfactory.

Abstract Background Pyrotinib, a novel irreversible tyrosine kinase inhibitor (TKI), has demonstrated promising antitumor activity to improve the overall response rate and progression-free survival (PFS) in patients with HER2-positive metastatic breast cancer (MBC). However, the survival data of pyrotinib or pyrotinib plus capecitabine in HER2-positive MBC remains scarce. Thus, we summarized the updated individual patient data from the phase I trials of pyrotinib or pyrotinib plus capecitabine, to provide a cumulative assessment on long-term outcomes and associated biomarker analysis of irreversible TKIs in HER2-positive MBC patients. Methods We performed a pooled analysis of the phase I trials for pyrotinib or pyrotinib plus capecitabine based on the updated survival data from individual patients. Next-generation sequencing was performed on circulating tumor DNA for predictive biomarkers. Results A total of 66 patients were enrolled, including 38 patients from the phase Ib trial for pyrotinib and 28 patients from the phase Ic trial for pyrotinib plus capecitabine. The median follow-up duration was 84.2 months (95% CI: 74.7–93.7 months). The estimated median PFS in the entire cohort was 9.2 months (95% CI: 5.4–12.9 months) and median OS was 31.0 months (95% CI: 16.5–45.5 months). The median PFS was 8.2 months in the pyrotinib monotherapy cohort and 22.1 months in the pyrotinib plus capecitabine group, while the median OS was 27.1 months in the pyrotinib monotherapy group and 37.4 months in the pyrotinib plus capecitabine group. Biomarker analysis suggested that the patients harbored concomitant mutations from multiple pathways in HER2-related signaling network (HER2 bypass signaling pathways, PI3K/Akt/mTOR pathway and TP53) were observed with significantly poorer PFS and OS when compared to those with none or one genetic alteration (median PFS, 7.3 vs. 26.1 months, P = 0.003; median OS, 25.1 vs. 48.0 months, P = 0.013). Conclusions The updated survival results based on individual patient data from the phase I trials of pyrotinib-based regimen revealed promising PFS and OS in HER2-positive MBC. Concomitant mutations from multiple pathways in HER2-related signaling network may be a potential efficacy and prognosis biomarker for pyrotinib in HER2-positive MBC. Trial registration ClinicalTrials.gov. (NCT01937689, NCT02361112).

Abstract Breast cancer has replaced lung cancer as the most common malignancy worldwide. The 5‐year survival rate of breast cancer has reached 90%. Systemic treatment of breast cancer has developed into a mature system including chemotherapy, targeted therapy, endocrine therapy and immunotherapy. This article summarizes the annual progress of breast cancer chemotherapy, targeted therapy, endocrine therapy and immunotherapy in 2022, providing valuable information for future research to better guide individualized treatment of breast cancer, thereby improving the prognosis and quality of life of breast cancer patients.

Abstract Purpose Patients with breast cancer are more likely to experience psychological distress than the general population. This study aimed to explore the relationship between depression and anxiety status measured before chemotherapy and adverse events during adjuvant chemotherapy in Chinese breast cancer patients. Methods This prospective study was conducted on 290 postoperative early‐stage breast cancer patients (response rate 96.7%) in China. Depression and anxiety status before adjuvant chemotherapy were assessed by the Hospital Anxiety and Depression Scale (HADS). Adverse events that occurred throughout the course of chemotherapy were graded and recorded according to Common Terminology Criteria for Adverse Events (CTCAE) 4.02. Results The rates of depression and anxiety were 20.0% and 31.4%, respectively, at baseline. The incidence of grade two or higher myelosuppression induced by chemotherapy was correlated with depression before chemotherapy (p = 0.037). Multivariate analysis showed that the incidence of myelosuppression was significantly related to depression before chemotherapy (p = 0.032). There was no association between depression and anxiety status and other adverse events (p > 0.05). Conclusions We observed an association between depression status in breast cancer patients receiving adjuvant chemotherapy and chemotherapy‐induced myelosuppression. Monitoring the depression status of breast cancer patients before chemotherapy may help to optimize the management of adverse events.

Background: Taxane-induced peripheral neuropathy (TIPN) is a debilitating adverse effect of cancer treatments with taxanes which may require a reduction or discontinuation chemotherapy and affect clinical and survival outcomes. A number of factors have contributed to the increasing prevalence of TIPN. Nonetheless, limited knowledge exists of potential prechemotherapy blood-based biochemical factors associated with TIPN development. Methods: We recruited breast cancer patients at seven cancer institutions in China. Participants aged 18 years or older with stage I to III breast cancer who scheduled to undergo primary neoadjuvant and adjuvant chemotherapy with taxanes were eligible. Eligible patients underwent patient-reported neuropathy assessments using the EORTC-CIPN20 questionnaire. Patients completed the questionnaire before commencing treatment and after every cycle. For every patient, we selected the highest TIPN toxicity score for analysis since the first cycle. The posttreatment TIPN severity was compared with blood-based biochemical factors within 30 days before commencing treatment. Independent samples t tests, Mann-Whitney U tests and linear regression were used to identify blood-based and clinical associations with TIPN development. Results: The study included 873 breast cancer participants who received paclitaxel, docetaxel or nanoparticle albumin-bound (nab)-paclitaxel. In the whole cohort, factors associated with higher TIPN toxicity scores were higher cumulative chemotherapy dose (β = 0.005; 95% CI, 0.004 to 0.006; P

Resveratrol is a polyphenolic compound with antioxidant and anti-inflammatory properties and therefore has potential health benefits for the prevention and treatment of a wide range of diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative diseases. The beneficial dose of resveratrol is between 30 and 150 mg. Although the health benefits of resveratrol have been extensively studied, resveratrol intake through the diet of residents in China remains unclear, which restricts the development of resveratrol-rich foods. In this study, a dietary assessment was conducted to reveal that the daily resveratrol intake by Chinese residents through common foods was only 0.783 mg, which was significantly below the beneficial dose. Among the main food types, fruits emerged as the primary source of resveratrol, contributing to 88.35% of the total intake. To improve resveratrol intake, potential methods to increase its consumption were proposed. First method is to increase the resveratrol content of fruits and peanuts. In addition, resveratrol can be extracted from peels. It is also recommended to adopt technical means to improve the bioavailability of resveratrol and develop related supplements and functional drinks.

Bladder pain is a prominent symptom in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We studied spinal mechanisms of bladder pain in mice using a model where repeated activation of intravesical Protease Activated Receptor-4 (PAR4) results in persistent bladder hyperalgesia (BHA) with little or no bladder inflammation. Persistent BHA is mediated by spinal macrophage migration inhibitory factor (MIF), and is associated with changes in lumbosacral proteomics. We investigated the contribution of individual spinal MIF receptors to persistent bladder pain as well as the spinal proteomics changes associated with relief of persistent BHA by spinal MIF antagonism. Female mice with persistent BHA received either intrathecal (i.t.) MIF monoclonal antibodies (mAb) or mouse IgG1 (isotype control antibody). MIF antagonism temporarily reversed persistent BHA (peak effect: 2 h), while control IgG1 had no effect. Moreover, i.t. antagonism of the MIF receptors CD74 and C-X-C chemokine receptor type 4 (CXCR4) partially reversed persistent BHA. For proteomics experiments, four separate groups of mice received either repeated intravesical scrambled peptide and sham i.t. injection (control, no pain group) or repeated intravesical PAR4 and: sham i.t.; isotype IgG1 i.t. (15 μg); or MIF mAb (15 μg). L6-S1 spinal segments were excised 2 h post-injection and examined for proteomics changes using LC-MS/MS. Unbiased proteomics analysis identified and relatively quantified 6739 proteins. We selected proteins that showed significant changes compared to control (no pain group) after intravesical PAR4 (sham or IgG i.t. treatment) and showed no significant change after i.t. MIF antagonism. Six proteins decreased during persistent BHA (V-set transmembrane domain-containing protein 2-like confirmed by immunohistochemistry), while two proteins increased. Spinal MIF antagonism reversed protein changes. Therefore, spinal MIF and MIF receptors mediate persistent BHA and changes in specific spinal proteins. These novel MIF-modulated spinal proteins represent possible new targets to disrupt spinal mechanisms that mediate persistent bladder pain.

Background: The relative lack of specifically targeted agents for HER2-negative metastatic breast cancer (MBC) makes the need for new agents or combination therapies to maximize clinical benefit while reducing toxicity critical. Objectives: To retrospectively analyze the efficacy and safety of eribulin combined with antiangiogenic drugs in the treatment of Chinese women with HER2-negative MBC. Methods: A total of 85 consecutive MBC patients with HER2-negative who were treated with eribulin + antiangiogenic agents between October 2020 and April 2023 in four institutions were retrospectively included in this study. Patients received eribulin 1.4 mg/m 2 (day 1 and 8) plus bevacizumab 7.5 mg/kg (day 1, 64 patients) or anlotinib 10 mg daily (day 1–14, 16 patients) or apatinib 250 mg daily (5 patients) on a 21-day cycle until progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS), according to Response Evaluation Criteria in Solid tumors (RECIST) 1.1. Secondary end-points included toxicities, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study included 85 HER2-negative MBC patients, with 41 patients (48.2%) in the first to second line group and 44 patients (51.8%) in the greater than or equal to third line group. The median age was 54.0 years. Thirty patients in the first to second line group and 14 patients in the greater than or equal to third line group had triple-negative breast cancer (TNBC). The ORR and DCR were 34.1% (29/85) and 75.3% (64/85). The median PFS (mPFS) of total population was 6.0 months (95% CI: 4.3–7.7), and median OS (mOS) was immature. The mPFS was 7.7 and 4.3 months in the first to second and greater than or equal to third line treatment ( p = 0.003), respectively. TNBC patients in first to second line therapy showed a significantly longer PFS (6.5 months versus 2.0 months, p = 0.021) compared to greater than or equal to third line. The incidences of cardiovascular toxicity were 29.4% in grades 1–2 and no grades 3–4. Hematologic toxicity (leukopenia and neutropenia) was the most common grade ⩾3 AEs, and AEs were more common in patients in greater than or equal to third line. Conclusion: The results suggest that eribulin combined with antiangiogenic therapy has a meaningful clinical activity and an acceptable safety profile in HER2-negative MBC.

Abstract Platinum‐based materials show excellent electrocatalytic performance and have good potential for use in fuel cells. However, the high cost and scarce reserves have restricted their wide application. Therefore, it is a challenging task to reduce the amount of Pt as well as ensure good catalytic performance. Herein, anchoring of Pt single atoms (0.21 wt‰) with ultra‐low content on g‐C3N4 nanosheets (Pt0.21/CN) has been successfully achieved. The obtained Pt0.21/CN catalyst shows excellent two‐electron oxygen reduction (2e− ORR) capability for hydrogen peroxide (H2O2). Compared with CN, its H2O2 selectivity increased from 80% to 98% in 0.1 M KOH, surpassing those in most of the reported studies. Besides, the H2O2 production rate of Pt0.21/CN is 767 mmol gcat−1 h−1, which is 11.1 times that of CN. This work may pave the way toward the development of an effective method for the design of noble‐metal electrocatalysts with low metal loading and high catalytic activity.

Product development projects usually contain many interrelated activities with complex information dependences, which induce activity rework, project delay and cost overrun. To reduce negative impacts, scheduling interrelated activities in an appropriate sequence is an important issue for project managers. This study develops a double-decomposition based parallel branch-and-prune algorithm, to determine the optimal activity sequence that minimizes the total feedback length (FLMP). This algorithm decomposes FLMP from two perspectives, which enables the use of all available computing resources to solve subproblems concurrently. In addition, we propose a result-compression strategy and a hash-address strategy to enhance this algorithm. Experimental results indicate that our algorithm can find the optimal sequence for FLMP up to 27 activities within 1 h, and outperforms state of the art exact algorithms.