Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality.

Importance: Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective: To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants: This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures: PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures: All-cause mortality, cancer mortality, and cardiovascular mortality. Results: This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance: In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Canola bee pollen is an effective artificial diet additive for improving larval development of predatory coccinellids: a lesson from Harmonia axyridis.

BACKGROUND: Pollen is a common plant-derived food source for predatory ladybird beetles under field conditions, yet the potential for pollen to improve the quality of artificial diets remains largely unexplored. In this study, we developed three pollen diets by incorporating varying proportions of canola bee pollen (7.5%, 15.0% and 22.5% with 2.5%, 5.0%, and 7.5% of water, respectively) into a conventional diet. The feeding efficiency of Harmonia axyridis, an omnivorous predator, was evaluated and compared on three pollen diets, a conventional nonpollen diet and pea aphids. RESULTS: The larvae fed a medium or high pollen diet exhibited significantly higher survival in the 4th instar, pupa and adult stages than those fed a nonpollen diet. These larvae also developed into significantly heavier adults, and their survival rates in adulthood were comparable to those fed pea aphids. Specifically, we revealed the underlying mechanisms through which a high pollen diet enhances pupal development. Consumption of high pollen diet versus nonpollen diet resulted not only in a significant decrease in pupal glycogen content, but also an increase in adult lipid content. Both diet treatments induced similar changes in carbohydrate and glycogen content compared to the aphid diet while exhibiting different alterations in pupal protein content and adult lipid content. Furthermore, the transcriptome analysis revealed that the nutrient metabolism, immune response, and cuticle development pathways were predominantly enriched among the differentially expressed genes (DEGs). CONCLUSION: Canola bee pollen offers diverse advantages in terms of rearing H. axyridis larvae with an artificial diet, which will advance the development of effective diets for predaceous coccinellids. © 2024 Society of Chemical Industry.

In Situ S-Doping Engineering for Highly Efficient NH3-SCR over Metal-Free Carbon Catalysts: A Novel Synergetic Promotional Mechanism.

Cyclic desulfurization-regeneration-denitrification based on metal-free carbon materials is one of the most promising ways to remove NOx and SO2 simultaneously. However, the impact of S-doping induced by the cyclic desulfurization and regeneration (C-S-R) process on the selective catalytic reduction (SCR) is not well understood. Herein, it is demonstrated that the C-S-R process at 500 °C induces in situ S-doping with a significant accumulation of C-S-C structures. NOx conversion was dramatically enhanced from 18.95% of the original sample to 84.55% of the S-doped sample. Density functional theory calculations revealed that the C-S-C structure significantly regulates the electronic structure of the C atom adjacent to the ketonic carbonyl group, thereby significantly altering the NH3 adsorption configuration with superior adsorption capacity. Moreover, S-doping induces an extra electron transfer between the N atom of the NH3 molecule and the C atom of the carbon plane, thereby promoting the activation of NH3 over the ketonic carbonyl group with a reduced energy barrier. This study elucidates a synergetic promotional mechanism between the ketonic carbonyl group and the C-S-C structure for SCR, offering a novel design strategy for high-performance heteroatom-doped carbon catalysts in industrial applications.

Outcomes of Robotic Versus Laparoscopic Pancreatoduodenectomy Following Learning Curves of Surgeons: A Multicenter Study on 2255 Patients.

OBJECTIVE: This study aimed to compare robotic pancreatoduodenectomy (RPD) with laparoscopic pancreatoduodenectomy (LPD) in operative and oncologic outcomes. BACKGROUND: Previous studies comparing RPD with LPD have only been carried out in small, single-center studies with variable quality. METHODS: Consecutive patients from nine centers in China who underwent RPD or LPD between 2015 and 2022 were included. A 1:1 propensity score matching (PSM) was used to minimize bias. RESULTS: Of the 2,255 patients, 1158 underwent RPD and 1097 underwent LPD. Following PSM, 1006 patients were enrolled in each group. The RPD group had significantly shorter operative time (270.0 vs. 305.0 minutes, P<0.001), lower intraoperative blood transfusion rate (5.9% vs. 12.0%, P<0.001), lower conversion rate (3.8% vs. 6.7%, P=0.004), and higher vascular reconstruction rate (7.9% vs. 5.6%, P=0.040) than the LPD group. There were no significant differences in estimated blood loss, postoperative length of stay, perioperative complications, and 90-day mortality. Patients who underwent vascular reconstruction had similar outcomes between the two groups, although they had significantly lower estimated blood loss (300.0 vs. 360.0 mL; P=0.021) in the RPD group. Subgroup analysis on pancreatic ductal adenocarcinoma (PDAC) found no significant differences between the two groups in median recurrence-free survival (14.3 vs. 15.3 mo, P=0.573) and overall survival (24.1 vs. 23.7 mo, P=0.710). CONCLUSIONS: In experienced hands, both RPD and LPD are safe and feasible procedures with similar surgical outcomes. RPD had the perioperative advantage over LPD especially in vascular reconstruction. For PDAC patients, RPD resulted in similar oncological and survival outcomes as LPD.

Monthly variations of groundwater arsenic risk under future climate scenarios in 2081-2100.

The seasonal variations of shallow groundwater arsenic have been widely documented. To gain insight into the monthly variations and mechanisms behind high groundwater arsenic and arsenic exposure risk in different climate scenarios, the monthly probability of high groundwater arsenic in Hetao Basin was simulated through random forest model. The model was based on arsenic concentrations obtained from 566 groundwater sample sites, and the variables considered included soil properties, climate, topography, and landform parameters. The results revealed that spatial patterns of high groundwater arsenic showed some fluctuations among months under different future climate scenarios. The probability of high total arsenic and trivalent arsenic was found to be elevated at the start of the rainy season, only to rapidly decrease with increasing precipitation and temperature. The probability then increased again after the rainy season. The areas with an increased probability of high total arsenic and trivalent arsenic and arsenic exposure risk under SSP126 were typically found in the high-arsenic areas of 2019, while those with decreased probabilities were observed in low-arsenic areas. Under SSP585, which involves a significant increase in precipitation and temperature, the probability of high total arsenic and trivalent arsenic and arsenic exposure risk was widely reduced. However, the probability of high total arsenic and trivalent arsenic and arsenic exposure risk was mainly observed in low-arsenic areas from SSP126 to SSP585. In conclusion, the consumption of groundwater for human and livestock drinking remains a threat to human health due to high arsenic exposure under future climate scenarios.

Low-Voltage Solution-Processed Zinc-Doped CuI Thin Film Transistors with NOR Logic and Artificial Synaptic Function.

Low-voltage Zn-doped CuI thin film transistors (TFTs) gated by chitosan dielectric were fabricated at a low temperature. The Zn-doped CuI TFT exhibited a more superior on/off current ratio than CuI TFT due to the substitution or supplementation of copper vacancies by Zn ions. The Zn-doped CuI films were characterized by scanning electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy. The Zn-doped CuI TFTs exhibited an on/off current ratio of 1.58 × 104, a subthreshold swing of 70 mV/decade, and a field effect mobility of 0.40 cm2V-1s-1, demonstrating good operational stability. Due to the electric-double-layer (EDL) effect and high specific capacitance (17.3 µF/cm2) of chitosan gate dielectric, Zn-doped CuI TFT operates at a voltage below -2 V. The threshold voltage is -0.2 V. In particular, we have prepared Zn-doped CuI TFTs with two in-plane gates and NOR logic operation is implemented on such TFTs. In addition, using the ion relaxation effect and EDL effect of chitosan film, a simple pain neuron simulation is realized on such a p-type TFTs for the first time through the bottom gate to regulate the carrier transport of the channel. This p-type device has promising applications in low-cost electronic devices, complementary electronic circuit, and biosensors.

Anti-Poisoning Mechanisms of Sb on Vanadia-Based Catalysts for NOx and Chlorobenzene Multi-Pollutant Control.

Modulating vanadia-based metal oxides is one of the effective methods for designing difunctional catalysts for simultaneous control of NOx and chlorobenzene (CB) from the emissions of industrial sources. Excessive NH3 adsorption and polychlorinated species accumulation on the surface are the primary issues poisoning catalysts and reducing their lifetime. Herein, Sb is selected as an NH3 adsorption alleviator and polychlorinated species preventor dopant on V2O5-WO3/TiO2. The catalyst exhibits an excellent performance for total NOx and 90% CB conversions at 300-400 °C under a gas hourly space velocity (GHSV) of 60,000 mL g-1 h-1. The HCl and N2 selectivities are maintained at 90 and 98%, respectively. The anti-poisoning ability could be attributed to the generated V-O-Sb chains on the surface: the band gap of vanadium is narrowed and the electron capability is strengthened. The above variation weakens the Lewis acid sites and blocks the electrophilic chlorination reactions of the catalyst surface (formation of polychlorinated species). In addition, oxygen vacancies on Sb-O-Ti also increase: the ring opening of benzoates is accelerated and NH3 adsorption energy is weakened. The above variation lowers the energy barriers of C-Cl cleavage even under NH3 pre-adsorption models and enhances NOx reduction thermodynamically and kinetically.

Robotic versus laparoscopic surgery for sporadic benign insulinoma: Short- and long-term outcomes.

BACKGROUND: Minimally invasive surgery is the optimal treatment for insulinoma. The present study aimed to compare short- and long-term outcomes of laparoscopic and robotic surgery for sporadic benign insulinoma. METHODS: A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was conducted. The demographic, perioperative and postoperative follow-up results were compared between the laparoscopic and robotic groups. RESULTS: A total of 85 patients were enrolled, including 36 with laparoscopic approach and 49 with robotic approach. Enucleation was the preferred surgical procedure. Fifty-nine patients (69.4%) underwent enucleation; among them, 26 and 33 patients underwent laparoscopic and robotic surgery, respectively. Robotic enucleation had a lower conversion rate to laparotomy (0 vs. 19.2%, P = 0.013), shorter operative time (102.0 vs. 145.5 min, P = 0.008) and shorter postoperative hospital stay (6.0 vs. 8.5 d, P = 0.002) than laparoscopic enucleation. There were no differences between the groups in terms of intraoperative blood loss, the rates of postoperative pancreatic fistula and complications. After a median follow-up of 65 months, two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a recurrence. CONCLUSIONS: Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time, which might lead to a reduction in postoperative hospital stay.

Deep-learning visualization enhancement method for optical coherence tomography angiography in dermatology.

Optical coherence tomography angiography (OCTA) in dermatology usually suffers from low image quality due to the highly scattering property of the skin, the complexity of cutaneous vasculature, and limited acquisition time. Deep-learning methods have achieved great success in many applications. However, the deep learning approach to improve dermatological OCTA images has not been investigated due to the requirement of high-performance OCTA systems and difficulty of obtaining high-quality images as ground truth. This study aims to generate proper datasets and develop a robust deep learning method to enhance the skin OCTA images. A swept-source skin OCTA system was employed to create low-quality and high-quality OCTA images with different scanning protocols. We propose a model named vascular visualization enhancement generative adversarial network and adopt an optimized data augmentation strategy and perceptual content loss function to achieve better image enhancement effect with small amount of training data. We demonstrate the superiority of the proposed method in skin OCTA image enhancement by quantitative and qualitative comparisons.

Genome-Wide Identification and Expression Analysis of NCED Gene Family in Pear and Its Response to Exogenous Gibberellin and Paclobutrazol.

The 9-cis-epoxycarotenoid dioxygenase (NCED) is a key enzyme for the process of ABA synthesis that plays key roles in a variety of biological processes. In the current investigation, genome-wide identification and comprehensive analysis of the NCED gene family in 'Kuerle Xiangli' (Pyrus sinkiangensis Yu) were conducted using the pear genomic sequence. In total, nineteen members of PbNCED genes were identified from the whole genome of pear, which are not evenly distributed over the scaffolds, and most of which were focussed in the chloroplasts. Sequence analysis of promoters showed many cis-regulatory elements, which presumably responded to phytohormones such as abscisic acid, auxin, etc. Synteny block indicated that the PbNCED genes have experienced strong purifying selection. Multiple sequence alignment demonstrated that these members are highly similar and conserved. In addition, we found that PbNCED genes were differentially expressed in various tissues, and three PbNCED genes (PbNCED1, PbNCED2, and PbNCED13) were differentially expressed in response to exogenous Gibberellin (GA3) and Paclobutrazol (PP333). PbNCED1 and PbNCED13 positively promote ABA synthesis in sepals after GA3 and PP333 treatment, whereas PbNCED2 positively regulated ABA synthesis in ovaries after GA3 treatment, and PbNCED13 positively regulated ABA synthesis in the ovaries after PP333 treatment. This study was the first genome-wide report of the pear NCED gene family, which could improve our understanding of pear NCED proteins and provide a solid foundation for future cloning and functional analyses of this gene family. Meanwhile, our results also give a better understanding of the important genes and regulation pathways related to calyx abscission in 'Kuerle Xiangli'.

A global transition to flash droughts under climate change.

Flash droughts have occurred frequently worldwide, with a rapid onset that challenges drought monitoring and forecasting capabilities. However, there is no consensus on whether flash droughts have become the new normal because slow droughts may also increase. In this study, we show that drought intensification rates have sped up over subseasonal time scales and that there has been a transition toward more flash droughts over 74% of the global regions identified by the Intergovernmental Panel on Climate Change Special Report on Extreme Events during the past 64 years. The transition is associated with amplified anomalies of evapotranspiration and precipitation deficit caused by anthropogenic climate change. In the future, the transition is projected to expand to most land areas, with larger increases under higher-emission scenarios. These findings underscore the urgency for adapting to faster-onset droughts in a warmer future.

Early and late recurrence patterns of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: a multicenter study.

BACKGROUND: Survival after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) remains poor because of high incidences of recurrence. The risk factors, patterns, and long-term prognosis in patients with early recurrence and late recurrence (ER and LR) for PDAC after PD were studied. METHODS: Data from patients who underwent PD for PDAC were analyzed. Recurrence was divided into ER (ER ≤1 years) and LR (LR >1 years) using the time to recurrence after surgery. Characteristics and patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with ER and LR. RESULTS: Among the 634 patients, 281 (44.3%) and 249 (39.3%) patients developed ER and LR, respectively. In the multivariate analysis, preoperative CA19-9 levels, resection margin status, and tumor differentiation were significantly associated with both ER and LR, while lymph node metastasis and perineal invasion were associated with LR. Patients with ER, when compared with patients with LR, showed a significantly higher proportion of liver-only recurrence ( P <0.05), and worse median PRS (5.2 vs. 9.3 months, P <0.001). Lung-only recurrence had a significantly longer PRS when compared with liver-only recurrence ( P <0.001). Multivariate analysis demonstrated that ER and irregular postoperative recurrence surveillance were independently associated with a worse prognosis ( P <0.001). CONCLUSION: The risk factors for ER and LR after PD are different for PDAC patients. Patients who developed ER had worse PRS than those who developed LR. Patients with lung-only recurrence had a significantly better prognosis than those with other recurrent sites.

[Cloning and expression analysis of JrGI gene in walnut].

GI (GIGANTEA) is one of the output key genes for circadian clock in the plant. The JrGI gene was cloned and its expression in different tissues was analyzed to facilitate the functional research of JrGI. RT-PCR (reverse transcription-polymerase chain reaction) was used to clone JrGI gene in present study. This gene was then analyzed by bioinformatics, subcellular localization and gene expression. The coding sequence (CDS) full length of JrGI gene was 3 516 bp, encoding 1 171 amino acids with a molecular mass of 128.60 kDa and a theoretical isoelectric point of 6.13. It was a hydrophilic protein. Phylogenetic analysis showed that JrGI of 'Xinxin 2' was highly homologous to GI of Populus euphratica. The result of subcellular localization showed that JrGI protein was located in nucleus. The JrGI, JrCO and JrFT genes in female flower buds undifferentiated and early differentiated of 'Xinxin 2' were analyzed by RT-qPCR (real-time quantitative PCR). The results showed that the expression of JrGI, JrCO and JrFT genes were the highest on morphological differentiation, implying the temporal and special regulation of JrGI in the differential process of female flower buds of'Xinxin 2'. In addition, RT-qPCR analysis showed that JrGI gene was expressed in all tissues examined, whereas the expression level in leaves was the highest. It is suggested that JrGI gene plays a key role in the development of walnut leaves.

Remote sensing of atmospheric and soil water stress on ecosystem carbon and water use during flash droughts over eastern China.

Flash droughts are often accompanied by large soil and atmospheric moisture deficits, and the concurrence of flash droughts and high temperature may have a great impact on the ecosystem. However, the stress of soil and atmospheric moisture deficits on carbon and water use of the ecosystem during flash droughts, especially during the drought periods with hot conditions, are unclear over a large region. In this study, we decoupled the atmospheric and soil water stress over eastern China by using vegetation productivity data and photosynthetically active radiation data retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS). The analysis is conducted during flash droughts and their sub-periods that are accompanied by high temperature and intense radiation from 2003 to 2018. The results showed that soil moisture (SM) stress was significantly greater than the vapor pressure deficit (VPD) stress on vegetation productivity in the humid regions of eastern China during flash droughts. However, high VPD controlled the water stress on light use efficiency (LUE) of vegetation over 55 % of the regions. For the hot periods of flash droughts, the area subjected to VPD stress on vegetation productivity significantly increased in semi-arid and semi-humid regions. The concurrent hot and drought conditions also increased water use efficiency (WUE) for most areas, which suggests that the reduction percentage of vegetation productivity is larger than that of evapotranspiration. Our research emphasized the severe impact of compound hot and flash drought conditions on vegetation carbon and water use from a remote sensing perspective.

Incorporating Exercise Efficiency to Evaluate the Accessibility and Capacity of Medical Resources in Tibet, China.

Accessibility and capacity of medical resources are key for the health care and emergency response, while the efficiency of the medical resources is very much limited by hypoxia in Tibet, China. Through introducing exercise efficiency, this study explores the accessibility of township residence to county-ship medical resources in Tibet using weighted mean travel time (WMT), and evaluates the medical capacity accordingly. The results show that: 1) the average travel time of township residence to county-level hospital is around 2 h by motor vehicle in Tibet. More than half of the population can not reach the county-ship hospital within 1 h, 33.24% of the population can not reach within 2 h, and 3.75% of the population can not reach within 6 h. 2) When considering the catchment of the medical resources and the population size, the WMT of the county-ship medical resources ranges from 0.25 h to 10.92 h. 3) After adjusted by travel time and exercise efficiency, the county-ship medical capacity became more unequal, with 38 out of 74 counties could not meet the national guideline of 1.8 medical beds per 1000. 4) In total, there are 17 counties with good WMT and sufficient medical resources, while 13 counties having very high WMT and low capacity of medical resources in Tibet. In the end, suggestions on medical resources relocation and to improve the capacity are provided. This study provides a method to incorporate exercise efficiency to access the accessibility and evaluate medical capacity that can be applied in high altitude ranges. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11769-022-1321-1.

Wastewater treatment by anodic oxidation in electrochemical advanced oxidation process: Advance in mechanism, direct and indirect oxidation detection methods.

Electrochemical Advanced Oxidation Process (EAOP) has been applied to the degradation of refractory pollutants in wastewater due to its strong oxidation capacity, high degradation efficiency, simple operation, and mild reaction. Among electrochemical processes, anodic oxidation (AO) is the most widely used and its mechanism is mainly divided into direct oxidation and indirect oxidation. Direct oxidation means that pollutants are oxidized at the anode by direct electron transfer. Indirect oxidation refers to the generation of active species during the electrolytic reaction, which acts on pollutants. The mechanism of AO process is controlled by many factors, including electrode type, electrocatalyst material, wastewater composition, pH, applied current and voltage levels. It is very important to explore the reaction mechanism of electrochemical treatment, which determines the efficiency of the reaction, the products of the reaction, and the extent of reaction. This paper firstly reviews the current research progress on the mechanism of AO process, and summarizes in detail the different mechanisms caused by influencing factors under common AO process. Then, strategies and methods to distinguish direct oxidation and indirect oxidation mechanisms are reviewed, such as intermediate product analysis, electrochemical test analysis, active species detection, theoretical calculation, and the limitations of these methods are analyzed. Finally some suggestions are put forward for the study of the mechanism of electrochemical advanced oxidation.

Evolution of the PEBP gene family in Juglandaceae and their regulation of flowering pathway under the synergistic effect of JrCO and JrNF-Y proteins.

Phosphatidyl ethanolamine-binding protein (PEBP) has a conserved PEBP domain and plays an important role in regulating the flowering time and growth of angiosperms. To understand the evolution of PEBP family genes in walnut family and the mechanism of regulating flowering in photoperiod pathway, 53 genes with PEBP domain were identified from 5 Juglandaceae plants. The PEBP gene family of Juglandaceae can be divided into four subgroups, FT-like, TFL-like, MFT-like and PEBP-like subgroups. These genes all show very high homology for motifs and gene structure in Juglandaceae. In addition, the results of gene replication and collinearity analysis showed that the evolution of PEBP genes was mainly purified and selected, and segmental repetition was the main driving force for the evolution of PEBP gene family in walnut family. We found that PEBP gene family played an important role in female flower bud differentiation, and most JrPEBP genes were highly expressed in leaf bud and female flower bud by qRT-PCR. In Arabidopsis, AtCO can not only directly bind to CORE2, but also interact with NF-Y complex to positively regulate the expression of AtFT gene. In this study, we proved that JrCO (the lineal homologue of AtCO) could not directly regulate the expression of JrFT gene, but could enhance the binding of JrNF-YB4/6 protein to the promoter of JrFT gene by forming a heteropolymer with NF-YB4/NF-YB6. We also confirmed that JrNF-YC1/3/7, JrNF-YB4/6 and JrCO can form a trimer structure similar to AtNF-YB-YC-CO of Arabidopsis, and then bind to the promoter of JrFT gene to promote the transcription of JrFT gene. In a word, through identification and analysis of PEBP gene family in Juglandaceae and study on the mechanism of photoperiod pathway regulating flowering in walnut, we have found that nuclear transcription factor NF-YB/YC plays a more important role in the trimer structure of NF-YB-YC-CO in walnut species. Our study has further perfected the flowering regulatory network of walnut species.

Combined immunotherapy for metastatic triple-negative breast cancer based on PD-1/PD-L1 immune checkpoint blocking.

Metastatic triple negative breast cancer is not only the worst prognosis and the strongest invasive subtype of breast cancer, but also the most immunogenic subtype, so it can be reasonably predicted that immunotherapy can play a positive role in the treatment of metastatic triple negative breast cancer. However, the effect of using PD-1/PD-L1 immune checkpoint inhibitors alone is not very ideal. In recent years, the regimen of combined therapy has been emerging. This article reviews the application of combined immunotherapy based on PD-1/PD-L1 inhibitors in metastatic triple negative breast cancer, including chemotherapy, targeted therapy, radiotherapy and oncolytic virus therapy. The problems existing in combined therapy and the possibility of future research are discussed, which can provide a reference for the selection of treatment options for patients with metastatic triple negative breast cancer in different situations.