BioPred: An R package for biomarkers analysis in precision medicine.

SUMMARY: The R package BioPred offers a suite of tools for subgroup and biomarker analysis in precision medicine. Leveraging Extreme Gradient Boosting (XGBoost) along with propensity score weighting and A-learning methods, BioPred facilitates the optimization of individualized treatment rules (ITR) to streamline subgroup identification. BioPred also enables the identification of predictive biomarkers and obtaining their importance rankings. Moreover, the package provides graphical plots tailored for biomarker analysis. This tool enables clinical researchers seeking to enhance their understanding of biomarkers and patient population in drug development. AVAILABILITY AND IMPLEMENTATION: The package is available at CRAN and https://github.com/deeplearner0731/BioPred. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Efficient removal of per- and polyfluoroalkyl substances (PFASs) from stored rainwater by composite metal salt /polydimethyldiallylammonium chloride coagulants.

Stored rainwater, the primary source of drinking water in the villages and towns of the Loess Plateau in northwest China, has been found to contain per- and polyfluoroalkyl substances (PFASs) and lacks necessary treatment measures. Coagulation is a common water treatment process, and enhancing its efficacy in removing PFASs can significantly improve treatment efficiency, reduce costs, and minimize the environmental and health risks associated with perfluorinated compounds. This study investigated the removal efficiency of perfluorobutanoic acid (PFBA), perfluorobutanesulfonic acid (PFBS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) using inorganic salt coagulants alone and in combination with polydimethyldiallylammonium chloride (PDMDAAC). The results indicated that the removal efficiencies of the four PFASs by polyferric chloride (PFCl) and polyaluminum chloride (PACl) increased with alkalinity. PDMDAAC significantly enhanced the coagulation removal efficiency of the four PFASs. The removal efficiency of the four PFASs was highest when the raw water pH was near 7. Within the molecular weight range of 0 to 500,000 for PDMDAAC, the removal efficiency of the four PFASs increased with increasing molecular weight. Charge neutralization is the primary coagulation mechanism for the removal of anionic PFASs. Therefore, this study provides guidance for selecting coagulants to remove PFASs from stored rainwater.

A circuit from lateral hypothalamic to dorsal hippocampal dentate gyrus modulates behavioral despair in mice.

Behavioral despair is one of the clinical manifestations of major depressive disorder and an important cause of disability and death. However, the neural circuit mechanisms underlying behavioral despair are poorly understood. In a well-established chronic behavioral despair (CBD) mouse model, using a combination of viral tracing, in vivo fiber photometry, chemogenetic and optogenetic manipulations, in vitro electrophysiology, pharmacological profiling techniques, and behavioral tests, we investigated the neural circuit mechanisms in regulating behavioral despair. Here, we found that CBD enhanced CaMKIIα neuronal excitability in the dorsal dentate gyrus (dDG) and dDGCaMKIIα neurons involved in regulating behavioral despair in CBD mice. Besides, dDGCaMKIIα neurons received 5-HT inputs from median raphe nucleus (MRN) and were mediated by 5-HT1A receptors, whereas MRN5-HT neurons received CaMKIIα inputs from lateral hypothalamic (LH) and were mediated by AMPA receptors to regulate behavioral despair. Furthermore, fluvoxamine exerted its role in resisting behavioral despair through the LH-MRN-dDG circuit. These findings suggest that a previously unidentified circuit of LHCaMKIIα-MRN5-HT-dDGCaMKIIα mediates behavioral despair induced by CBD. Furthermore, these support the important role of AMPA receptors in MRN and 5-HT1A receptors in dDG that might be the potential targets for treatment of behavioral despair, and explain the neural circuit mechanism of fluvoxamine-resistant behavioral despair.

PM2.5 prediction based on modified whale optimization algorithm and support vector regression.

In order to obtain the pattern of variation of PM2.5concentrations in the atmosphere in Nanchang City, we build a Support Vector Regression(SVR) with modified Whale Optimization Algorithm(WOA) hybrid model (namely mWOA-SVR model) that can predict the PM2.5concentration. Firstly, according to the Pearson correlation coefficient (PCC) method to examine the dynamic relationship between air pollutants and meteorological factors together with them, PM10, SO2and CO were selected as air pollutant concentration characteristics, while daily maximum and minimum temperatures, and wind power levels were selected as meteorological characteristics; then, using modified WOA algorithm for parameter selection of SVR model, four sets of better parameter combinations were found; finally, the mWOA-SVR model was built by the four sets parameters to predict PM2.5concentration. The results show that the prediction accuracy of mixed mWOA-SVR model with pollutant concentration plus weather factors as the feature was higher than single pollutant concentration.

Study on confined interface electron enhanced ethanol to hydrogen conversion by Rhodopseudomonas palustris.

Conjugated polymer coatings enhance bacteria with eco-friendly energy use. A new hybrid system boosts hydrogen production by Rhodopseudomonas palustris@polypyrrole (R. palustris@PPy) through interface electron transfer and hydrogel encapsulation. To maximize the output, we studied hydrogen metabolism using various techniques and found that conductive polymer modification facilitated electron transfer, affecting intracellular pathways. This technology offers enhanced green hydrogen production for sustainable energy.

Expanding the Color Range of Photoresponsive Multicolor Luminescent System Through Host-Guest Interaction.

Photoresponsive multicolor luminescent systems offer interesting functions, which have led to applications in anticounterfeiting and biological imaging. However, expanding the color range of these materials remains a challenging task. Herein, a carbazole-modified dithienylethene derivative (DTE-CZ) that exhibits modulated fluorescence color changes through the photocyclization reaction and photolysis reaction is synthesized. DTE-CZ emits orange fluorescence, and it can release a fluorophore which emits blue fluorescence by the photolysis reaction, resulting in the color change. Upon complexation of DTE-CZ with cucurbit[10]uril (CB[10]), the fluorescence wavelength will have a blue shift and the photolysis reaction will be inhibited. Benefiting from the influence of CB[10] and the photolysis reaction of free guests, the color range of the photoresponsive system which is composed of free guests and host-guest complexes is further extended. White light emission along with a color shift from yellow-green to blue was achieved by adjusting the ratio of free guests to host-guest complexes. Finally, the photoresponsive multicolor systems are utilized to construct a photostimulated PVA film and an information encryption system. This work provides an alternative strategy for the preparing of photoresponsive multicolor luminescent system and modulation of its color range.

Construction and validation of a nomogram prediction model for the catheter-related thrombosis risk of central venous access devices in patients with cancer: a prospective machine learning study.

Central venous access devices (CVADs) are integral to cancer treatment. However, catheter-related thrombosis (CRT) poses a considerable risk to patient safety. It interrupts treatment; delays therapy; prolongs hospitalisation; and increases the physical, psychological and financial burden of patients. Our study aims to construct and validate a predictive model for CRT risk in patients with cancer. It offers the possibility to identify independent risk factors for CRT and prevent CRT in patients with cancer. We prospectively followed patients with cancer and CVAD at Xiangya Hospital of Central South University from January 2021 to December 2022 until catheter removal. Patients with CRT who met the criteria were taken as the case group. Two patients with cancer but without CRT diagnosed in the same month that a patient with cancer and CRT was diagnosed were selected by using a random number table to form a control group. Data from patients with CVAD placement in Qinghai University Affiliated Hospital and Hainan Provincial People's Hospital (January 2023 to June 2023) were used for the external validation of the optimal model. The incidence rate of CRT in patients with cancer was 5.02% (539/10 736). Amongst different malignant tumour types, head and neck (9.66%), haematological (6.97%) and respiratory (6.58%) tumours had the highest risks. Amongst catheter types, haemodialysis (13.91%), central venous (8.39%) and peripherally inserted central (4.68%) catheters were associated with the highest risks. A total of 500 patients with CRT and 1000 without CRT participated in model construction and were randomly assigned to the training (n = 1050) or testing (n = 450) groups. We identified 11 independent risk factors, including age, catheterisation method, catheter valve, catheter material, infection, insertion history, D-dimer concentration, operation history, anaemia, diabetes and targeted drugs. The logistic regression model had the best discriminative ability amongst the three models. It had an area under the curve (AUC) of 0.868 (0.846-0.890) for the training group. The external validation AUC was 0.708 (0.618-0.797). The calibration curve of the nomogram model was consistent with the ideal curve. Moreover, the Hosmer-Lemeshow test showed a good fit (P > 0.05) and high net benefit value for the clinical decision curve. The nomogram model constructed in this study can predict the risk of CRT in patients with cancer. It can help in the early identification and screening of patients at high risk of cancer CRT.

Effect of deep testosterone reduction on the prognosis of metastatic prostate cancer with high-volume disease.

OBJECTIVE: This study aims to investigate the correlation between serum testosterone levels after one month of treatment and prognosis in patients with high-volume disease metastatic prostate cancer (mPCa) who are undergoing combined androgen blockade therapy (CAB). METHODS: The clinical data of 199 patients with high-volume disease mPCa, diagnosed through biopsy pathology and imaging, were retrospectively analyzed from January 2010 to October 2022 in the Department of Urology at the First Affiliated Hospital of Xinjiang Medical University. Among these patients, 111 cases had a deep reduction in serum testosterone (< 0.7 nmol/l) after one month of treatment, while 88 cases did not achieve a deep reduction (≥ 0.7 nmol/l). The study utilized the Kaplan-Meier method to plot survival curves and employed the multifactor COX regression model to analyze independent risk factors. The risk factors with a significance level of P < 0.05 in the multivariate analysis were included in the nomogram prediction model. The accuracy of the model was assessed using the ROC curve and the calibration curve, while the net benefit for patients was evaluated through the decision curve analysis (DCA). RESULTS: The group that achieved deep testosterone reduction(DTR) had a higher proportion of PSA < 0.2 ng/ml and a greater PSA decline rate after six months of treatment (P < 0.05). The group that achieved DTR and the group that did not achieve DTR had a progression to castration resistant prostate cancer(CRPC) time of 17.93 ± 6.68 months and 13.43 ± 6.12 months, respectively (P < 0.001). The median progression-free survival time for the 2 groups were 18 months and 12 months, respectively (P < 0.001). The median overall survival times were 57 months and 32 months, respectively (P < 0.001). The median progression-free survival times were 18, 15, and 10 months for the group that achieved DTR within 1 month, the group that achieved DTR beyond 1 month but within 1 year, and the group that did not achieve DTR within 1 year, respectively (P < 0.001), and the median survival times were 57, 45, and 26 months, respectively (P < 0.001). COX multivariate analysis revealed that a testosterone level of ≥ 0.7 nmol/l at 1 month of treatment is an independent risk factor for the progression to CRPC and prognosis in patients with high-volume disease mPCa (P < 0.05). The risk of death in patients with a testosterone level of ≥ 0.7 nmol/l at 1 month of treatment was 2.087 times higher than that of patients with a level of < 0.7 nmol/l (P < 0.05). A nomogram prediction model was developed using independent risk factors, with the area under the ROC curve (AUC) for progression-free survival (PFS) at 12, 15, 18, and 21 months being 0.788, 0.772, 0.760, and 0.739, respectively. For 3 and 5 years, the AUCs for overall survival (OS) were 0.691 and 0.624. The calibration curve demonstrated good consistency between the model's predicted values and the actual outcomes. CONCLUSION: Patients with high-volume disease mPCa who receive CAB treatment may experience extended progression-free survival and overall survival if their serum testosterone levels are below 0.7 nmol/l after one month of treatment. The longer it takes to achieve DTR, the worse the patient's prognosis may be. The nomogram prediction model developed in this study demonstrates good predictive ability in assessing the progression and prognosis of high-volume disease mPCa.

White rot fungi as a multifaceted biocontrol agent: Metabolic disruption and algal inhibition in Microcystis aeruginosa.

Microcystis aeruginosa is a prevalent cyanobacterium linked to water eutrophication and harmful algal blooms. While bacterial control strategies are well-studied, the effects of white rot fungi on Microcystis aeruginosa are less understood. This study examines the impact of whole fungal liquid, its centrifuged supernatant, and sterilized solutions on the algae's physiological and biochemical traits. Metabolomics and multivariate analysis identified significant changes in 47 metabolic markers, including carbohydrates, amino acids, and fatty acids, across treatments. The complete fungal liquid exhibited the strongest algicidal effect, likely due to synergistic solubilization mechanisms mediated by extracellular enzymes such as manganese peroxidase, catalase, and laccase. Notably, algicidal activity persisted even after sterilization, suggesting the presence of non-proteinaceous compounds like polysaccharides or lipids. The metabolic disturbances included downregulation of the TCA cycle and reduced fatty acid synthesis, leading to inhibited photosynthesis and compromised nucleic acid integrity in the algal cells. This research enhances our understanding of how white rot fungi disrupt Microcystis aeruginosa metabolism, providing a theoretical basis for their potential use in bioremediation of eutrophic aquatic environments.

Biofortifying multiple micronutrients and decreasing arsenic accumulation in rice grain simultaneously by expressing a mutant allele of OAS-TL gene.

Rice grains typically contain relatively high levels of toxic arsenic (As) but low levels of essential micronutrients. Biofortification of essential micronutrients while decreasing As accumulation in rice would benefit human nutrition and health. We generated transgenic rice expressing a gain-of-function mutant allele astol1 driven by the OsGPX1 promoter. astol1 encodes a plastid-localized O-acetylserine (thiol) lyase (OAS-TL) with Ser189Asn substitution (OsASTOL1S189N), which enhances cysteine biosynthesis by forming an indissociable cysteine synthase complex with its partner serine acetyltransferase (SAT). The effects on growth, As tolerance, and nutrient and As accumulation in rice grain were evaluated in hydroponic, pot and field experiments. The expression of OsASTOL1S189N in pOsGPX1::astol1 transgenic lines enhanced SAT activity, sulphate uptake, biosynthesis of cysteine, glutathione, phytochelatins and nicotianamine, and enhanced tolerance to As. The expression of OsASTOL1S189N decreased As accumulation while increased the accumulation of multiple macronutrients (especially sulphur, nitrogen and potassium) and micronutrients (especially zinc and selenium) in rice grain in a pot experiment and two field experiments, and had little effect on plant growth and grain yield. Our study provides a new strategy to genetically engineer rice to biofortify multiple essential nutrients, reducing As accumulation in rice grain and enhancing As tolerance simultaneously.

Exposure of cumulative atherogenic index of plasma and the development of prediabetes in middle-aged and elderly individuals: evidence from the CHARLS cohort study.

BACKGROUND: The impact of dynamic changes in the degree of atherosclerosis on the development of prediabetes remains unclear. This study aims to investigate the association between cumulative atherogenic index of plasma (CumAIP) exposure during follow-up and the development of prediabetes in middle-aged and elderly individuals. METHODS: A total of 2,939 prediabetic participants from the first wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. The outcomes for these patients, including progression to diabetes and regression to normal fasting glucose (NFG), were determined using data from the third wave. CumAIP was calculated as the ratio of the average AIP values measured during the first and third waves to the total exposure duration. The association between CumAIP and the development of prediabetes was analyzed using multivariable Cox regression and restricted cubic spline (RCS) regression. RESULTS: During a median follow-up period of 3 years, 15.21% of prediabetic patients progressed to diabetes, and 22.12% regressed to NFG. Among the groups categorized by CumAIP quartiles, the proportion of prediabetes progressing to diabetes gradually increased (Q1: 10.61%, Q2: 13.62%, Q3: 15.65%, Q4: 20.95%), while the proportion regressing to NFG gradually decreased (Q1: 23.54%, Q2: 23.71%, Q3: 22.18%, Q4: 19.05%). Multivariable-adjusted Cox regression showed a significant positive linear correlation between high CumAIP exposure and prediabetes progression, and a significant negative linear correlation with prediabetes regression. Furthermore, in a stratified analysis, it was found that compared to married individuals, those who were unmarried (including separated, divorced, widowed, or never married) had a relatively higher risk of CumAIP-related diabetes. CONCLUSION: CumAIP is closely associated with the development of prediabetes. High CumAIP exposure not only increases the risk of prediabetes progression but also hinders its regression within a certain range. These findings suggest that monitoring and maintaining appropriate AIP levels may help prevent the deterioration of blood glucose levels.

Lipase activated endocytosis-like behavior of oil-in-water emulsion.

Oil-in-water emulsion is a system with extensive applications in foods, cosmetics and coating industries, and it could also be designed into an artificial lipid droplet in recent works. However, the insights into the biophysical dynamic behaviors of such artificial lipid droplets are lacking. Here, we reveal an enzymatic reaction triggered endocytosis-like behavior in the oil-in-water emulsion lipid droplets. A thermodynamically favored recruitment of lipases onto the membrane of the droplets is demonstrated. We confirm that the hydrolysis of tributyrin by lipases can decrease the interfacial tension and increase the compressive force on the membrane, which are the two main driving forces for triggering the endocytosis-like behavior. The endocytosis-like behavior induced various emerging functionalities of the lipid droplets, including proteins, DNA or inorganic particles being efficiently sequestered into the oil droplet with reversible release as well as enhanced cascade enzymatic reaction. Overall, our studies are expected to open up a way to functionalize oil-in-water emulsions capable of life-inspired behaviors and tackle emerging challenges in bottom-up synthetic biology, revealing the unknown dynamic behaviors of lipid droplets in living organisms.

In silico prediction of drug-induced nephrotoxicity: current progress and pitfalls.

INTRODUCTION: Due to its role in absorption and metabolism, the kidney is an important target for drug toxicity. Drug-induced nephrotoxicity (DIN) presents a significant challenge in clinical practice and drug development. Conventional methods for assessing nephrotoxicity have limitations, highlighting the need for innovative approaches. In recent years, in silico methods have emerged as promising tools for predicting DIN. AREAS COVERED: A literature search was performed using PubMed and Web of Science, from 2013 to February 2023 for this review. This review provides an overview of the current progress and pitfalls in the in silico prediction of DIN, which discusses the principles and methodologies of computational models. EXPERT OPINION: Despite significant advancements, this review identified issues accentuates the pivotal imperatives of data fidelity, model optimization, interdisciplinary collaboration, and mechanistic comprehension in sculpting the vista of DIN prediction. Integration of multiple data sources and collaboration between disciplines are essential for improving predictive models. Ultimately, a holistic approach combining computational, experimental, and clinical methods will enhance our understanding and management of DIN.

Characterization of a ferroptosis-related gene signature predicting survival and immunotherapeutic response in lung adenocarcinoma.

Lung cancer remains the leading cause of cancer-related death worldwide, and drug resistance represents the main obstacle responsible for the poor mortality and prognosis. Here, to identify a novel gene signature for predicting survival and drug response, we jointly investigated RNA sequencing data of lung adenocarcinoma patients from TCGA and GEO databases, and identified a ferroptosis-related gene signature. The signature was validated in the validation set and two external cohorts. The high-risk group had a reduced survival than the low-risk group (P < 0.05). Moreover, the established gene signature was associated with tumor mutation burden, microsatellite instability, and response to immune checkpoint blockade. In addition, four candidate oncogenes (RRM2, SLC2A1, DDIT4, and VDAC2) were identified to be candidate oncogenes using in silico and wet experiments, which could serve as potential therapeutic targets. Collectively, this study developed a novel ferroptosis-related gene signature for predicting prognosis and drug response, and identified four candidate oncogenes for lung adenocarcinoma.

Oxygen- and proton-transporting open framework ionomer for medium-temperature fuel cells.

Medium-temperature proton exchange membrane fuel cells (MT PEMFCs) operating at 100° to 120°C have improved kinetics, simplified thermal and water management, and broadened fuel tolerance compared with low-temperature PEMFCs. However, high temperatures lead to Nafion ionomer dehydration and exacerbate gas transportation limitations. Inspired by osmolytes found in hyperthermophiles, we developed α-aminoketone-linked covalent organic framework (COF) ionomers, interwoven with Nafion, to act as "breathable" proton conductors. This approach leverages synergistic hydrogen bonding to retain water, enhancing hydration and proton transport while reducing oxygen transport resistance. For commercial Pt/C, the MT PEMFCs achieved peak and rated power densities of 18.1 and 9.5 Watts per milligram of Pt at the cathode at 105°C fueled with H2 and air, marking increases of 101 and 187%, respectively, compared with cells lacking the COF.

Preoperative HIFU ablation combined with femoral bone marrow nailing for the treatment of pathological fracture of femur: a case report.

Introduction and importance: Bone is one of the common sites of metastasis in lung cancer. Pathological fractures of the femur significantly reduce patients' quality of life and increase the risk of death. However, there is still no consensus on the optimal treatment of pathological femoral fractures. The authors' report provides a treatment method for a patient with pathological fracture of lung cancer with preoperative HIFU lesion ablation followed by combined intramedullary nail fixation. Case presentation: A 61-year-old Chinese woman was hospitalized with severe pain in her right thigh. X-ray and CT examination at admission considered pathological fracture of the right femur. MRI showed a comminuted fracture of the middle and lower part of the right femur, swelling of the surrounding soft tissue, and effusion. WBS showed an abnormal concentration of imaging agent at the right femoral fracture end and abnormal bone metabolism. After a lung biopsy, it was diagnosed as lung cancer with femoral metastasis and pathological fracture. Clinical discussion: The patient underwent HIFU ablation before surgery to reduce the lesion, and a re-examination MRI showed that the signal at the lesion was significantly reduced, and the lesion volume was significantly reduced. The operation was performed by open reduction and intramedullary nail fixation, focal excision, and bone cement filling. After 6 months of follow-up, the patient's bone metastasis was not aggravated, and there was no loosening or fracture of the right femoral intramedullary nail. Conclusion: This is a case of pathological fracture of the femur caused by bone metastases from pulmonary cancer. The patient used HIFU to reduce the lesion before the operation and combined it with intramedullary nail internal fixation to treat the pathological fracture. A satisfactory therapeutic effect was obtained. The authors believe that this is a safe and effective treatment. This case may be beneficial to the treatment of pathological fracture of bone metastasis of lung cancer.

Specific static and dynamic functional network connectivity changes in thyroid-associated ophthalmopathy and it predictive values using machine learning.

Background: Thyroid-associated ophthalmopathy (TAO) is a prevalent autoimmune disease characterized by ocular symptoms like eyelid retraction and exophthalmos. Prior neuroimaging studies have revealed structural and functional brain abnormalities in TAO patients, along with central nervous system symptoms such as cognitive deficits. Nonetheless, the changes in the static and dynamic functional network connectivity of the brain in TAO patients are currently unknown. This study delved into the modifications in static functional network connectivity (sFNC) and dynamic functional network connectivity (dFNC) among thyroid-associated ophthalmopathy patients using independent component analysis (ICA). Methods: Thirty-two patients diagnosed with thyroid-associated ophthalmopathy and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. ICA method was utilized to extract the sFNC and dFNC changes of both groups. Results: In comparison to the HC group, the TAO group exhibited significantly increased intra-network functional connectivity (FC) in the right inferior temporal gyrus of the executive control network (ECN) and the visual network (VN), along with significantly decreased intra-network FC in the dorsal attentional network (DAN), the default mode network (DMN), and the left middle cingulum of the ECN. On the other hand, FNC analysis revealed substantially reduced connectivity intra- VN and inter- cerebellum network (CN) and high-level cognitive networks (DAN, DMN, and ECN) in the TAO group compared to the HC group. Regarding dFNC, TAO patients displayed abnormal connectivity across all five states, characterized by notably reduced intra-VN connectivity and CN connectivity with high-level cognitive networks (DAN, DMN, and ECN), alongside compensatory increased connectivity between DMN and low-level perceptual networks (VN and basal ganglia network). No significant differences were observed between the two groups for the three dynamic temporal metrics. Furthermore, excluding the classification outcomes of FC within VN (with an accuracy of 51.61% and area under the curve of 0.35208), the FC-based support vector machine (SVM) model demonstrated improved performance in distinguishing between TAO and HC, achieving accuracies ranging from 69.35 to 77.42% and areas under the curve from 0.68229 to 0.81667. The FNC-based SVM classification yielded an accuracy of 61.29% and an area under the curve of 0.57292. Conclusion: In summary, our study revealed that significant alterations in the visual network and high-level cognitive networks. These discoveries contribute to our understanding of the neural mechanisms in individuals with TAO, offering a valuable target for exploring future central nervous system changes in thyroid-associated eye diseases.

A prospective single arm cohort study: An analysis of the effectiveness of surgical treatment of locally advanced breast cancer.

Background: Breast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10-15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. Method: We conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. Results: Between March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. Conclusion: Patients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins.

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2'-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

Responses of ecosystem service trade-offs and synergies in Guangfo Metropolitan Area to multidimensional expansion of urban space.

Understanding the responses of ecosystem service trade-offs and synergies in metropolitan areas to the multidimensional expansion of urban space is of great significance for the optimization of regional land spatial pattern and high-quality development. With the Guangfo Metropolitan Area as research region, we used land use data and natural ecological environment data from 2000 to 2020 to measure the expansion characteristics of urban space in the dimensions of scale, distribution, and morphology by using the landscape pattern indices. We further calculated four main ecosystem services: urban cooling, habitat quality, recreation, and water conservation by the InVEST model, quantified the trade-off and synergistic relationship of multiple ecosystem services by the coupling coordination degree model, and explored its response to multidimensional urban spatial expansion by using the multi-scale geographically weighted regression model. The results showed that urban land use scale in the Guangfo Metropolitan Area continued to increase from 2000 to 2020, with an accelerated growth rate from 2010 to 2020. The ave-rage patch area of urban land in the central area and the urban land of small patches in the northeast increased, evolving from a "dual-center" structure to a "single-center" one. The distance between urban land patches in the Guangfo Metropolitan Area was relatively small, indicating a compact distribution of urban land. The distance between newly developed urban land patches was also small, but had gradually increased in recent years. The patch shape of urban land was relatively regular and less complex, but the complexity of the newly added urban land gra-dually increased. The ecosystem service trade-offs and synergies in the Guangfo Metropolitan Area had undergone significant changes, with a decrease in synergies and an increase in trade-off, and extreme trade-offs had gradually become dominant. The response of ecosystem services synergies to changes in urban land use scale was the most intense and had spatial heterogeneity, while the response to the change of distribution and morphological characte-ristics of urban land showed periodic differences.