The efficacy of adjuvant chemotherapy in patients with different midpoint-radiotherapy Epstein-Barr virus DNA plasma loads.

OBJECTIVES: This study aimed to evaluate the efficacy of adjuvant chemotherapy (AC) in patients with different midpoint-radiotherapy (mid-RT) Epstein-Barr virus (EBV) DNA plasma loads for locoregionally advanced nasopharyngeal carcinoma (NPC), and to provide decision-making regarding the use of AC. MATERIALS AND METHODS: A total of 675 consecutive patients diagnosed with stage III-IVa NPC were enrolled in this study. All patients underwent concurrent chemoradiotherapy (CCRT), either with or without induction chemotherapy or AC, or a combination of both. The primary endpoint of this study was progression-free survival (PFS). RESULTS: Among the 675 enrolled patients, 248 (36.7 %) received AC and 427 (63.3 %) were only observed after CCRT. In total, 149 (22.1 %) patients had detectable mid-RT EBV DNA levels, whereas 526 (77.9 %) had undetectable mid-RT EBV DNA levels. Patients with detectable mid-RT EBV DNA had worse 5-year PFS than those with undetectable mid-RT EBV DNA (74.8 % vs. 81.9 %, P = 0.045). AC group showed significantly better 5-year PFS than observation in patients with detectable mid-RT EBV DNA (82.8 % vs. 66.8 %; HR, 0.480; 95 % CI 0.250-0.919, P = 0.027). Multivariate analyses demonstrated that the treatment methods (AC vs. observation) were independent prognostic factors for PFS (HR, 0.37; 95 % CI 0.19-0.74, P = 0.005). However, in patients with undetectable mid-RT EBV DNA (5-year PFS: HR 0.873, 95 % CI 0.565-1.349, P = 0.52), AC group showed no survival benefit for observation. CONCLUSION: AC could reduce the risk of disease progression compared to observation in patients with detectable mid-RT EBV DNA. Our findings suggest that AC is effective in patients at a high risk of treatment failure.

How has carbon storage changed in the Yili-Tianshan region over the past three decades and into the future? What has driven it to change?

Predicting future land use changes and assessing carbon storage remain challenging. Nowadays, how nature and socioeconomics drive changes in carbon storage is a hot topic in research. In this study, through the projection of land use type and the integration of the PLUS, Integrated Valuation of Ecosystem Services and Trade-offs (InVEST), and Geodetector models, we constructed a framework for assessing carbon storage in different land use scenarios. Utilizing this framework, it is possible to project land use change and estimate carbon storage based on different development scenarios. We applied the framework to the Yili Tianshan region and identified the main driving forces for carbon storage change. Further, we estimated the carbon storage in the Yili Tianshan region in 2035 under four scenarios (RE, NE, EP, and CLP). The results showed the following: 1) Between 1990 and 2020, there was an increase in the forest area and water bodies in the Yili-Tianshan region, mainly from bare land. 2) As shown on the time scale, carbon storage increases in the Yili-Tianshan region with a W-shaped fluctuation by converting grasslands and bare land into forests. On a spatial scale, the carbon storage was lower in the center and higher on both sides in the Yili-Tianshan region. 3) In 2035- RE, 2035-ND, and 2035-EP scenarios, the carbon storage was increased by 4.30 Tg, 6.67 Tg, and 12.08 Tg; in the 2035-CLP scenario, it was decreased by 14.63 Tg. The Yili-Tianshan region experienced a notable rise in carbon storage under the 2035-EP scenario compared to the other three scenarios. 4) Soil type played a significant role in the spatial differentiation of carbon storage in Yili-Tianshan (q value 0.5958), followed by population density (0.5394). The changes in carbon storage in the Yili-Tianshan region are the result of synergistic effects of multiple factors, in which the soil type∩soil erosion intensity are the most important. This research could provide a reference method for improving regional carbon storage.

[Seasonal variation of water utilization sources and responses to precipitation in the dominant species of broad-leaved and needle-leaved mixed forests in Mount Lushan, China]. / 庐山针阔混交林优势种水分利用来源季节变化及对降水的响应.

Elucidating the seasonal patterns of water sources for dominant species in the sub-tropical humid mountainous forest, analyzing the eco-hydrological complementarity and competition mechanisms among coexisting species, investigating the responses of plant water utilization to precipitation, could provide a theoretical basis for vegetation restoration and management. Based on the stable hydrogen and oxygen isotope technique, we analyzed the δ2H and δ18O characteristics of precipitation, xylem water from Pinus massoniana and Quercus variabilis, and soil water from 0-100 cm depth in Mount Lushan, China. The MixSIAR model, Levins index, and PS index were used to calculate the relative contribution rate of each water source, the hydrological niche breadth, and niche overlap of P. massoniana and Q. variabilis. The results showed that, in the wet season (March to July), P. massoniana primarily utilized soil water from the 0-20 cm and 20-40 cm depths, while Q. variabilis primarily utilized that from the 20-40 cm and 40-60 cm depths. During the dry season (August to September), P. massoniana and Q. variabilis utilized 40-60 cm and 60-80 cm of soil water, respectively, resulting in an increase in the depth of water absorption. In the early growing season (March to April) and the late growing season (September), there was a high hydrological niche overlap between P. massoniana and Q. variabilis, resulting in intensitive water competition. In the middle of the growing season (May to August), the water source was adequately allocated, and the hydrolo-gical niche was segregated to meet the high transpiration demand. Q. variabilis primarily utilized soil water from a depth of 60-80 cm and 60-80 cm before a precipitation event, and from a depth of 0-20 cm and 20-40 cm after the event. In contrast, P. massoniana primarily utilized soil water from a depth of 0-20 cm and 20-40 cm both before and after a precipitation event. In conclusion, water utilization patterns of P. massoniana and Q. variabilis exhibited a seasonal trend, with shallow water uptake during the rainy season and deep water uptake during the dry season. These species are capable of efficiently allocating water resources during the peak growth season, and their root systems actively respond to change in soil moisture level. They have strong adaptability to extreme precipitation events and exhibit remarkable water conservation capabilities.

[Clinical observation of minimally invasive extraction of lower third molar by retaining the buccal bone plate].

PURPOSE: To explore the effect of extracting the completely impacted teeth by minimally invasive surgery with preserving the buccal bone plate. METHODS: Eighty-six cases were selected and randomly divided into 2 groups. In the experimental group, a fenestration was made with a ball drill to expose the buccal and lingual margin of crown, and the buccal bone plate was preserved. T-shaped crown cuttings were performed, minimally invasive extraction was conducted.In the control group, the distal and buccal bone plates were removed with a ball drill, the distal and buccal crowns were exposed, and T-shaped crown was cut. The other procedures were the same. The degree of swelling, restricted mouth opening and VAS pain score after operation were observed, the levels of C-reactive protein and anti-hemolytic streptoglobulin were detected by laboratory tests, and the periodontal probing depth(PD), bleeding index (BI), and clinical attachment loss(CAL) of the adjacent second molar were examined 1 month after surgery. SPSS 25.0 software package was used for data analysis. RESULTS: The swelling degree of the two groups was significantly relieved in the experimental group than in the control group (P＜0.05), and there was no significant difference in the degree of mouth opening limitation and pain (P＞0.05). The level of C-reactive protein in the control group was significantly higher than that in the observation group (P＜0.05). There was no significantly difference in the level of anti-hemolytic streptococcus between the 2 groups (P＞0.05). One month after operation, the PD and CAL in the control group were significantly higher than those in the experimental group(P＜0.05). There was no significant difference between the 2 groups in BI(P＞0.05). CONCLUSIONS: The patients who preserve the buccal bone plate by minimally invasive extraction of impacted mandibular teeth have less reaction and better wound healing.

[Ecological Environment Assessment and Driving Mechanism Analysis of Nagqu and Amdo Sections of Qinghai-Xizang Highway Based on Improved Remote Sensing Ecological Index].

The ecological environment along the Qinghai-Xizang highway is an important part of the construction of the ecological civilization in the Xizang region, and current research generally suffers from difficulties in data acquisition, low timeliness, and failure to consider the unique "alpine saline" environmental conditions in the study area due to the unique geographical environment of the Qinghai-Xizang plateau. Based on the GEE platform and the unique geographical environment of the study area, the remote sensing ecological index (RSEI) was improved, and a new saline remote sensing ecological index (SRSEI) applicable to the alpine saline region was constructed by using principal component analysis as an ecological environment quality evaluation index. The spatial distribution pattern and temporal variation trend of ecological environment quality along the Qinghai-Xizang Highway Nagqu-Amdo section were analyzed at multiple spatial and temporal scales using the ArcGIS 10.3 platform and geographic probes, and the driving mechanisms of eight control factors, including natural and human-made, on the spatial and temporal changes in SRSEI were investigated. The results showed that:① compared with RSEI, SRSEI was more sensitive to vegetation and had a stronger discriminatory ability in areas with sparse vegetation and severe salinization, which is suitable for ecological quality evaluation in alpine saline areas. ② The spatial scale of ecological environment quality in the study area had obvious geographical differentiation, and the areas with poor ecological quality were mainly concentrated in the northern Amdo County, whereas the areas with excellent and good quality grades were mainly distributed in the central-western and southeastern Nagqu areas. On the temporal scale, the ecological environment of the study area as a whole showed an improvement trend over 32 years, and the vegetation cover in the central-western and southeastern areas increased significantly, which had a strong improvement effect on the ecological environment. The improvement area was 1 425.98 km2, accounting for 99.82%. The mean value of SRSEI was 0.49, with an overall fluctuating upward trend and an average increase of 0.015 7 a-1. ③ The land use pattern was the most driving influence factor in the change of ecological environment quality in the study area, with an average q value of 0.157 6 over multiple years, and the influence of environmental factors was low. The multi-factor interaction results showed that the ecological environment in the study area was the result of multiple factors acting together, all factors had synergistic enhancement under the interaction, the influence of human factors was gradually increasing, and the interaction of the net primary productivity (NPP) of vegetation and land use pattern was the main interactive control factor of ecological environment quality in the study area. This study can provide a theoretical basis for ecological environmental protection and sustainable development along the Nagqu to Amdo section.

Reduced-dose radiotherapy for Epstein-Barr virus DNA selected staged III nasopharyngeal carcinoma: A single-arm, phase 2 trial.

BACKGROUND: Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC). PATIENTS AND METHODS: We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov, number NCT03668730. RESULTS: One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%-94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8-46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%-98.9%) with a median follow-up of 43.9 months (IQR 40.2-46.2). The most common late toxicity was grade 1-2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months. CONCLUSION: Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC.

Research on the Prediction Model of Engine Output Torque and Real-Time Estimation of the Road Rolling Resistance Coefficient in Tracked Vehicles.

Road parameter identification is of great significance for the active safety control of tracked vehicles and the improvement of vehicle driving safety. In this study, a method for establishing a prediction model of the engine output torques in tracked vehicles based on vehicle driving data was proposed, and the road rolling resistance coefficient f was further estimated using the model. First, the driving data from the tracked vehicle were collected and then screened by setting the driving conditions of the tracked vehicle. Then, the mapping relationship between the engine torque Te, the engine speed ne, and the accelerator pedal position ß was obtained by a genetic algorithm-backpropagation (GA-BP) neural network algorithm, and an engine output torque prediction model was established. Finally, based on the vehicle longitudinal dynamics model, the recursive least squares (RLS) algorithm was used to estimate the f. The experimental results showed that when the driving state of the tracked vehicle satisfied the set driving conditions, the engine output torque prediction model could predict the engine output torque T^e in real time based on the changes in the ne and ß, and then the RLS algorithm was used to estimate the road rolling resistance coefficient f^. The average coefficient of determination R of the T^e was 0.91, and the estimation accuracy of the f^ was 98.421%. This method could adequately meet the requirements for engine output torque prediction and real-time estimation of the road rolling resistance coefficient during tracked vehicle driving.

Sorting of Cluster-Confined Metallic Single-Walled Carbon Nanotubes for Fabricating Atomically Vacant Uranium Oxide.

Single-walled carbon nanotube (SWCNT) heterostructures have shown great potential in catalysis, magnetism, and nanofluidics, in which host SWCNTs with certain conductivity (metallic or semiconducting) are highly required. Herein, inspired by the large molecular weight and redox properties of polyoxometalate (POM) clusters, we reported the selective separation of POM encapsulated metallic SWCNTs (POM@m-SWCNTs) with a uniform diameter through density gradient ultracentrifugation (DGU). The confined POMs increased the SWCNT density and amplified the nanotubes' density difference, thus greatly lowering the centrifugal force (70,000g) of DGU. With this strategy, a series of POM@m-SWCNTs of ∼1.2 nm with high purity were sorted. The mechanism supported by theoretical and experimental evidence showed that the separation of m-SWCNTs depended on not only nanotube/cluster size but also the conductivity of SWCNTs. The smallest 1.2 nm m-SWCNT that can exactly accommodate a 0.9 nm-{Mo6} cluster exhibited the maximum electron transfer to inner clusters; thus, intertube π-π stacking of such m-SWCNTs was greatly loosened, leading to the preferential dispersion into individual ones and partitioning in the uppermost layer after DGU. As a proof-of-concept application, this sorting strategy was extended to separate heavy-element 238U-encapsulated m-SWCNTs. The phase-pure, tiny (1-2.5 nm) U4O9 crystals with atomic vacancy clusters were fabricated on m-SWCNTs through growth kinetic control. This work may provide a general way to construct desired actinide materials on specific SWCNTs.

Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial.

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

Changes of Oral Flora, Inflammatory Factors, and Immune Function Indicators in Patients with Chronic Periodontitis and Their Clinical Significance.

This research focuses on investigating the changes of oral flora, inflammatory factors, and immune function indicators in patients with chronic periodontitis (CP) and their clinical significances. Clinical indices such as gingival index (GI) and sulcus bleeding index (SBI) of the study subjects were recorded. The levels of oral flora, inflammatory factors and T lymphocyte subsets in gingival crevicular fluid (GCF) of the study subjects were measured. To analyze the correlation between GI and gingival SBI and oral flora, inflammatory factors, and immune function indicators, Pearson correlation analysis was performed. Porphyromonas gingivalis, Streptococcus digestiveis, Prevotella intermedia, Veronococcus, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, CD3+, CD4+, and CD4+/CD8+ had a positive correlation with GI and SBI, while IL-10 and CD8+ were negatively correlated with GI and SBI. Oral flora, inflammatory factors and immune function indicators levels are largely elevated in patients with CP and they are correlated with CP clinical indicators.

Increased uptake of deep soil water promotes drought resistance in mixed forests.

The intensity and frequency of droughts are projected to rise in recent years and adversely affect forests. Thus, information on plant water use and acclimation during and after droughts is crucial. This study used the stable isotope and thermal dissipation probes to detect the water-use adaptation of mixed forests to drought using a precipitation gradient control experiment in the field. The results showed that Platycladus orientalis and Quercus variabilis mainly absorbed stable water from deep soil layers during the drought (32.05% and 28.2%, respectively). The synergetic nocturnal sap flow in both species replenished the water loss, but P. orientalis experienced a greater decline in transpiration acclimation to drought. The transpiration of Q. variabilis remained high since it was mainly induced by radiation. After short-term exposure to drought, P. orientalis majorly obtained shallow soil water, confirming its sensitivity to shallow water. Contrarily, Q. variabilis mainly absorbed stable water from deep soil layers regardless of the soil water content. Therefore, these findings suggest that Q. variabilis cannot physiologically adjust to extreme drought events, possibly limiting their future distributions and altering the composition of boreal forests.

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Clinical characteristics and prognostic factors affecting survival after radical radiotherapy for early and late post-treatment metastatic nasopharyngeal carcinoma.

OBJECTIVE: We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies. METHODS: This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan-Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models. RESULTS: The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease. CONCLUSIONS: The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.

Doping Effect on Mesoporous Carbon-Supported Single-Site Bifunctional Catalyst for Zinc-Air Batteries.

Rechargeable zinc-air batteries (ZABs) require bifunctional electrocatalysts presenting high activity in oxygen reduction/evolution reactions (ORR/OER), but the single-site metal-N-C catalysts suffer from their low OER activity. Herein, we designed a series of single-site Fe-N-C catalysts, which present high surface area and good conductivity by incorporating into mesoporous carbon supported on carbon nanotubes, to study the doping effect of N and P on the bifunctional activity. The additional P-doping dramatically increased the content of active pyridine-N and introduced P-N/C/O sites, which not only act as extra active sites but also regulate the electron density of Fe centers to optimize the absorption of oxygenated intermediates, thereby ultimately improving the bifunctional activity of Fe-N-C sites. The optimized catalyst displayed a half-wave potential of 0.882 V for ORR and a low overpotential of 365 mV at 10 mA cm-2 for OER, which significantly outperforms the counterpart without P, as well as noble-metal-based catalysts. The ZABs with air cathodes containing the N,P-co-doped catalysts exhibited a high peak power density of 201 mW cm-2 and a long cycling stability beyond 600 h. Doping has shown to be an effective way to optimize the performance of single-site catalysts in bifunctional oxygen electrocatalysis, which can be extended to other catalyst systems.

Apolipoprotein E*Ɛ2 carriers exhibit high aspirin-treated platelet reactivity and low cardiovascular risk during long-term aspirin treatment.

OBJECTIVE: Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. METHODS: A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. RESULTS: After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048-0.715, P = 0.014; HR = 0.435, CI: 0.234-0.812, P = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers. CONCLUSIONS: Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.

A multi-stable isotopic constraint on water column oxygen sinks in the Pearl River Estuary, South China.

Bottom water oxygen depletion is a central concern in estuaries and coastal oceans worldwide. However, a mechanistic understanding and quantitative diagnosis of different oxygen-consuming processes are less clear. In this study, a multi-stable isotope approach is developed to delineate the role of oxygen respiration and nitrification contributing to total oxygen consumption in the Pearl River Estuary (PRE), a large eutrophic estuary in south China. The approach highly couples with analysis of the carbon isotope composition of dissolved inorganic carbon (δ13C-DIC) and with stable nitrogen isotope analysis in ammonium (δ15N-NH4+) and nitrate (δ15N-NO3-). In all seasons, relatively low DO concentrations were observed in the upper reach and, to some extent, in the outer estuary during summer, while high concentrations of DO were found in the transition zone between the inner and outer estuary. On the basis of isotopic differentiation, our data reveal that much more depleted δ13C-DIC is coincident with DIC additions and low oxygen in the upper reach and inner estuary during most seasons. This is most likely a consequence of organic carbon (OC) degradation via aerobic respiration. Based on the carbon isotopic mass balance of DIC and the stoichiometry ratio of -ΔDO/ΔDIC, we found that the OC degradation dominates the total oxygen consumption in the upper reach, as well as in the inner estuary during summer (48.3%-93.5%). In addition, nitrification is another key process in contributing to total oxygen loss in the upper reach, as supported by the well-coupled variations of δ15N of NH4+ and NO3- and apparent oxygen utilization (AOU). Using the formerly determined N isotopic fractionation and observed δ15N variation, we estimated that nitrification could account for 35.3%-44.1% and 28.5%-31.6% of the total oxygen consumption in the upper reach during winter and summer, respectively, while its contribution to total oxygen loss is minor in the inner and outer estuary. Overall, this study demonstrates the potential of the multi-stable isotopic approach to assess oxygen sink partitioning in large human-perturbed estuaries.

EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) was the first oncogenic virus identified in humans. It is primarily associated with multiple lymphoid and epithelial cancers, including nasopharyngeal carcinoma (NPC). However, its association with ferroptosis and its role in cancer therapy resistance have not been fully elucidated. Here, we show that EBV infection reduces the sensitivity of NPC cells to ferroptosis by activating the p62-Keap1-NRF2 signaling pathway in conjunction with upregulation of SLC7A11 and GPX4 expression. Knockdown of endogenous GPX4 or blockade of GPX4 using a specific inhibitor enhanced the chemosensitivity of EBV-infected NPC cells. Functional studies revealed that GPX4 knockdown suppresses the proliferation and colony formation of NPC cells. Mechanistically, GPX4 interacts with the TAK1-TAB1/TAB3 complex, regulates TAK1 kinase activity, and further activates downstream MAPK-JNK and NFκB pathways. High GPX4 expression is correlated with poor clinical outcomes in patients with NPC and other cancer types. Taken together, our findings suggest that EBV infection has important effects on redox homeostasis, revealing a previously unappreciated role for GPX4 in tumor progression. This novel mechanism provides a potential new target for the treatment of EBV-related tumors.

Soil water stress overrides the benefit of water-use efficiency from rising CO2 and temperature in a cold semi-arid poplar plantation.

The counteractive effect of atmospheric CO2 (ca ) enrichment and drought stress on tree growth results in great uncertainty in the growth patterns of forest plantations in cold semi-arid regions. We analysed tree ring chronologies and carbon isotopes in Populus simonii plantations in cold semi-arid areas in northern China over the past four decades. We hypothesized that the hydraulic stress from drought would override the stimulating effect of increasing ca and temperature (T) on stem growth (basal area increment [BAI]). We found the stimulating effect of rising ca and T on the growth, indicated by continuous increase of intrinsic water-use efficiency in all stands and a positive correlation between T and BAI. However, these effects failed to alleviate the negative impacts of drought on tree growth. Concurrent acceleration of BAI reversed during the intensive drought episodes. Water stress resulted from inaccessibility of roots to deep soil water rather than from lack of precipitation, suggested by the decoupling of BAI from precipitation and vapour pressure deficit. Local soil water limitation might also cause greater stomatal regulation in declining trees, indicated by lower intercellular CO2 concentration. Thus, site-specific soil moisture conditions growth sensitivity to global warming resulting in site-specific decline episodes in drought-prone areas.

Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial.

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

Identifying distinct risks of treatment failure in nasopharyngeal carcinoma: Study based on the dynamic changes in peripheral blood lymphocytes, monocytes, N classification, and plasma Epstein-Barr virus DNA.

BACKGROUND: To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure. METHODS: A total of 1124 eligible patients with Stage II-IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated. RESULTS: Patients with high ΔALC% were correlated with poorer 5-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p < 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p < 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2-3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low-risk group [with <1 risk factor], intermediate risk group [with 1-3 risk factors], and high-risk group [with 4 risk factors]) that correlated with disparate risks of death (p < 0.001), disease progression (p < 0.001), and distant metastasis (p < 0.001). CONCLUSIONS: High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk-adapted therapeutic strategies for NPC.