Critical new insights into the interactions of hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) with albumin at molecular and cellular levels.

A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.

Prevalence of sleep disturbances in endometriosis patients: a systematic review and meta-analysis.

Objective: This study systematically analyzes the prevalence of sleep disturbance in patients with endometriosis. Methods: The PubMed, Web of Science, Embase, Wanfang, China National Knowledge Internet Database (CNKI), China Science and Technology Journal Database were searched from their establishment to January 2024, using the search terms endometriosis and sleep disturbance to collect relevant literature on the prevalence of sleep disturbance in patients with endometriosis. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. The prevalence of sleep disorders in patients with endometriosis was systematically analyzed using Stata17.0 software. Results: Sixteen studies with 2573 participants were included. The prevalence of sleep disturbance in patients with endometriosis was 70.8% (95% confidence interval: 60.7%~80.9%). The said prevalence was higher in China than in Iran and the European countries (78.2 vs. 57.6 vs. 64.4, Q=9.27, P=0.010) and increased significantly since 2018 (79.0 vs. 61.3, Q=3.97, P=0.046). This prevalence was significantly higher in the cohort study than that in cross-sectional and case-control studies (84.0 vs. 74.0 vs. 59.5, Q=7.16, P=0.028). Conclusion: The prevalence of sleep disturbance is high in patients with endometriosis, particularly in China and its prevalence has increased significantly in recent years. Appropriate interventions are recommended to effectively prevent or minimize sleep disturbances in patients with endometriosis.

Incidence and risk factors for amputation in Chinese patients with diabetic foot ulcers: a systematic review and meta-analysis.

Objective: This study aimed to comprehensively analyze the incidence of amputation in Chinese patients with diabetic foot ulcers (DFUs). Methods: The Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. The CNKI, Wanfang Data, VIP, PubMed, Web of Science, and Embase databases were searched to collect relevant literature on the incidence of amputation in Chinese patients with DFUs. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. The data were systematically analyzed using Stata 17.0 software to determine the incidence of amputation in this patient population. Results: A total of 25 papers were included in the study, revealing an incidence of amputation in Chinese patients with DFUs of 22.4% (95% confidence interval: 18.3-26.5%). The subgroup analysis revealed that a history of ulcers, Wagner grade >3, and diabetic peripheral vascular disease were the primary risk factors associated with a higher incidence of amputation in Chinese patients with DFUs (P<0.05). Among Chinese patients with DFUs, the amputation group and the non-amputation group showed significant differences in body mass index, duration of DFUs, total cholesterol, triglyceride, fasting blood glucose, white blood cell count, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and uric acid (P<0.05). Conclusion: The high incidence of amputation among Chinese patients with DFUs indicates that interventions should be implemented to prevent or minimize amputations. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023463976.

Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial.

Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036). Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

Increasing contamination of polycyclic aromatic hydrocarbons in Chinese soils.

China is facing a serious threat PAHs contaminated soil. To better understand the current state of soil PAH pollution in China and contribute to the development of feasible prevention and control measures and policies in the future. This study examines the spatiotemporal distributions of soil Polycyclic Aromatic Hydrocarbons (PAHs) pollution in China since 2000, and investigates the key factors influencing changes in levels of soil PAHs. The results of the survey on soil PAHs concentration levels in 716 areas were analyzed by visualization of ArcGIS pro data, correlation analysis and linear regression analysis, it was found that the increase in soil PAH pollution in China is concerning. The analysis indicates significant regional disparities, with pollution levels in the north being higher than in the south. Over the 20-year period, the median level of PAHs in soil increased by 476.8 µg/kg. Construction land areas that heavily rely on fossil fuels and industrial activities exhibit significantly higher concentrations of polycyclic aromatic hydrocarbons (PAHs) compared to other land use types. The study identifies key socio-economic factors linked to rising PAH levels, including energy consumption (notably coal and oil), industrial and domestic waste production. Coal consumption is highlighted as the leading factor in PAH concentration changes in 18 provinces, followed by industrial waste in 6 provinces. Future projections up to 2030 suggest continued influence of these factors on soil PAH levels. The research emphasizes the urgent necessity for comprehensive soil management policies to address the growing PAH pollution, offering insights into its dynamics and contributing factors in China.

Clonal growth characteristics and diversity patterns of different Clintonia udensis (Liliaceae) diploid and tetraploid cytotypes in the Hualongshan Mountains.

Polyploidization plays an important role in plant evolution and biodiversity. However, intraspecific polyploidy compared to interspecific polyploidy received less attention. Clintonia udensis (Liliaceae) possess diploid (2n = 2x = 14) and autotetraploid (2n = 4x = 28) cytotypes. In the Hualongshan Mountains, the autotetraploids grew on the northern slope, while the diploids grew on the southern slopes. The clonal growth characteristics and clonal architecture were measured and analyzed by field observations and morphological methods. The diversity level and differentiation patterns for two different cytotypes were investigated using SSR markers. The results showed that the clonal growth parameters, such as the bud numbers of each rhizome node and the ratio of rhizome branches in the autotetraploids were higher than those in the diploids. Both the diploids and autotetraploids appeared phalanx clonal architectures with short internodes between ramets. However, the ramets or genets of the diploids had a relatively scattered distribution, while those of the autotetraploids were relatively clumping. The diploids and autotetraploids all allocated more biomass to their vegetative growth. The diploids had a higher allocation to reproductive organs than that of autotetraploids, which indicated that the tetraploids invested more resources in clonal reproduction than diploids. The clone diversity and genetic diversity of the autotetraploids were higher than that of the diploids. Significant genetic differentiation between two different cytotypes was observed (P < 0.01). During establishment and evolution, C. udensis autotetraploids employed more clumping phalanx clonal architecture and exhibited more genetic variation than the diploids.

Automated segmentation of brain metastases with deep learning: a multi-center, randomized crossover, multi-reader evaluation study.

BACKGROUND: Artificial intelligence has been proposed for brain metastasis (BM) segmentation but it has not been fully clinically validated. The aim of this study was to develop and evaluate a system for BM segmentation. METHODS: A deep-learning-based BM segmentation system (BMSS) was developed using contrast-enhanced MR images from 488 patients with 10,338 brain metastases. A randomized crossover, multi-reader study was then conducted to evaluate the performance of the BMSS for BM segmentation using data prospectively collected from 50 patients with 203 metastases at five centers. Five radiology residents and five attending radiologists were randomly assigned to contour the same prospective set in assisted and unassisted modes. Aided and unaided Dice similarity coefficients (DSCs) and contouring times per lesion were compared. RESULTS: The BMSS alone yielded a median DSC of 0.91 (95% confidence interval, 0.90-0.92) in the multi-center set and showed comparable performance between the internal and external sets (p = 0.67). With BMSS assistance, the readers increased the median DSC from 0.87 (0.87-0.88) to 0.92 (0.92-0.92) (p < 0.001) with a median time saving of 42% (40-45%) per lesion. Resident readers showed a greater improvement than attending readers in contouring accuracy (improved median DSC, 0.05 [0.05-0.05] vs. 0.03 [0.03-0.03]; p < 0.001), but a similar time reduction (reduced median time, 44% [40-47%] vs. 40% [37-44%]; p = 0.92) with BMSS assistance. CONCLUSIONS: The BMSS can be optimally applied to improve the efficiency of brain metastasis delineation in clinical practice.

Spatial - temporal mapping of urine cadmium levels in China during 1980 - 2040: Dietary improvements lower exposure amid rising pollution.

Persistent cadmium exposure poses significant health risks to the Chinese population, underscored by its prevalence as an environmental contaminant. This study leverages a machine-learning model, fed with a comprehensive dataset of environmental and socio-economic factors, to delineate trends in cadmium exposure from 1980 to 2040. We uncovered that urinary cadmium levels peaked at 1.09 µg/g Cr in the mid-2000 s. Encouragingly, a decline is projected to 0.92 µg/g Cr by 2025, tapering further to 0.87 µg/g Cr by 2040. Despite this trend, regions heavily influenced by industrialization, such as Hunan and Guizhou, as well as industrial counties in Jilin, report stubbornly high levels of exposure. Our demographic analysis reveals a higher vulnerability among adults & adolescents over 14, with males displaying elevated cadmium concentrations. Alarmingly, the projected data suggests that by 2040, an estimated 41% of the population will endure exposure beyond the safety threshold set by the European Food Safety Authority. Our research indicates disproportionate cadmium exposure impacts, necessitating targeted interventions and policy reforms to protect vulnerable groups and public health in China.

Mapping Blood Lead Levels in China during 1980-2040 with Machine Learning.

Lead poisoning is globally concerning, yet limited testing hinders effective interventions in most countries. We aimed to create annual maps of county-specific blood lead levels in China from 1980 to 2040 using a machine learning model. Blood lead data from China were sourced from 1180 surveys published between 1980 and 2022. Additionally, regional statistical figures for 15 natural and socioeconomic variables were obtained or estimated as predictors. A machine learning model, using the random forest algorithm and 2973 generated samples, was created to predict county-specific blood lead levels in China from 1980 to 2040. Geometric mean blood lead levels in children (i.e., age 14 and under) decreased significantly from 104.4 µg/L in 1993 to an anticipated 40.3 µg/L by 2040. The number exceeding 100 µg/L declined dramatically, yet South Central China remains a hotspot. Lead exposure is similar among different groups, but overall adults and adolescents (i.e., age over 14), females, and rural residents exhibit slightly lower exposure compared to that of children, males, and urban residents, respectively. Our predictions indicated that despite the general reduction, one-fourth of Chinese counties rebounded during 2015-2020. This slower decline might be due to emerging lead sources like smelting and coal combustion; however, the primary factor driving the decline should be the reduction of a persistent source, legacy gasoline-derived lead. Our approach innovatively maps lead exposure without comprehensive surveys.

Urinary cadmium levels in China (1982-2021): Regional trends and influential factors.

Despite the significant threat of cadmium exposure in China, a national-level assessment has been conspicuously absent. This study bridges this critical gap by collecting, geospatial analyzing and multivariable regression analyzing published studies on urinary cadmium levels in Chinese from 1982 to 2021. Our research reveals a notable decline trend in cadmium exposure among Chinese populations. However, this trend varies by region, age and gender group, higher levels are seen in the South (1.04 µg/g cr) compared to the North (0.48 µg/g cr), and in adults (1.08 µg/g cr) relative to children (0.33 µg/g cr), with higher levels being more pronounced in females (6.17 µg/g cr). Urinary cadmium is significantly correlated with rice consumption (P < 0.001), while mining activities have been identified as the dominant factor for cadmium exposure in most regions of China, a trend that is evident both in past decades and is expected to continue into the next decade. These findings underscore the need for region-specific environmental and public health strategies, designed to effectively address the distinct cadmium exposure risks in various regions and among different population groups, thus enhancing protection against the adverse effects of cadmium.

High-efficiency fiber-cladding power stripper based on all-dielectric optical thin films.

Although conventional fiber-cladding power strippers (CPSs) based on the techniques of high-index adhesive or corrosive liquids onto fiber inner cladding have been well developed, they are still facing challenges in special applications such as spaceborne or radiation-environment fiber lasers and amplifiers. In this paper, we propose and fabricate high-efficiency CPSs based on all-dielectric optical thin films. By numerically analyzing the propagation characteristics of cladding light at the thin film interface, we design a high-index T a 2 O 5 CPS and A l 2 O 3 CPS with single- and cascaded-layer films coated onto the fiber inner cladding, respectively. In our experiment, the CPSs are successfully fabricated onto the inner-cladding surface of 10/125 double-clad fiber based on ion-beam-assisted deposition technology. The stripping efficiency for the 976 nm residual cladding power was measured up to 99.38%, and the stripping power of the fiber CPS without active cooling can be 24 W at least. Such CPS could be advantageous for applications in spaceborne-based fiber lasers or amplifiers (e.g., gravitational wave detection, spaceborne lidar).

Clinical characteristics and prognostic factors in nasopharyngeal carcinoma with brain metastasis: A retrospective, single-center study.

BACKGROUND: Brain metastasis is rare in nasopharyngeal carcinoma (NPC), with only anecdotal cases reported. Conducting a systematic study is crucial for improving the management of these patients. MATERIALS AND METHODS: Forty-one patients with brain metastasis were retrospectively included between February 2000 and February 2023. The clinical characteristics and treatment information of patients were analyzed. Overall survival (OS) was estimated by Kaplan-Meier survival analysis, and Cox proportional hazard regression analysis was performed to explore prognostic factors. RESULTS: The median OS for patients was 11.2 months, with a 3-year OS rate of 16.3%. The number of extracranial metastatic organs (HR = 5.533, P = 0.041) and the response of extracranial tumors to treatment (HR = 0.079, P = 0.003) were independent prognostic factors in the cohort. CONCLUSIONS: Brain metastasis in NPC is a devastating condition that commonly occurs through hematogenous dissemination. Systemic therapy remains fundamental treatment, while local therapy for brain metastases may further improve survival in selected patients.

The interaction of perfluorooctane sulfonate with hemoproteins and its relevance to molecular toxicology.

Perfluorooctane sulfonate (PFOS), a representative of perfluorinated compounds in industrial and commercial products, has posed a great threat to animals and humans via environmental exposure and dietary consumption. Herein, we investigated the effects of PFOS binding on the redox state and stability of two hemoproteins (hemoglobin (Hb) and myoglobin (Mb)). Fluorescence spectroscopy, circular dichroism and UV-vis absorption spectroscopy demonstrated that PFOS could induce the conformational changes of proteins along with the exposure of heme cavity and generation of hemichrome, which resulted in the increased release of free hemin. After that, free hemin liberated from hemoproteins led to reactive oxygen species formation, lipid peroxidation, cell membrane damage and loss of cell viability in vascular endothelial cells, while neither Hb nor Mb did show cytotoxicity. Chemical inhibitors of ferroptosis effectively mitigated hemin-caused toxicity, identifying the hemin-dependent ferroptotic cell death mechanisms. These data demonstrated that PFOS posed a potential threat of toxicity through a mechanism which involved its binding to hemoproteins, decreased oxygen transporting capacity, and increased hemin release. Altogether, our findings elucidate the binding mechanisms of PFOS with two hemoproteins, as well as possible risks on vascular endothelial cells, which would have important implications for the human and environmental toxicity of PFOS.

Serum albumin acted as an effective carrier to improve the stability of bioactive flavonoid.

The health-improving functions of bioactive flavonoids in vitro and in vivo are often limited by their low stability, which could be counteracted by the application of proteins as carriers of flavonoids. Clarification of the mechanism of protein-ligand interaction is crucial for the encapsulation of bioactive components. Herein, common plasma proteins [i.e., bovine serum albumin (BSA), human serum albumin (HSA), human immunoglobulin G (IgG) and fibrinogen (FG)] were compared for their binding characteristics to quercetin, the main component of flavonoids in human diet, in the absence and presence of free Cu2+ (an accelerator for flavonoids' instability) using multi-spectroscopic and computational methods. As a flexible open structure of proteins, both BSA and HSA were found to be the most promising carriers for quercetin and Cu2+ with an affinity on the order of 104 M-1. HSA-diligand complex (i.e., HSA-quercetin-Cu2+) was successfully generated when both quercetin and Cu2+ were added to the HSA solution. The stability and free radical scavenging activity of bioactive quercetin during incubation was promoted in the HSA-diligand complex relative to quercetin-Cu2+ complex. Quercetin/Cu2+ system could induce the formation of reactive oxygen species such as hydrogen peroxide (H2O2) and hydroxide radical (·OH), which were significantly suppressed upon HSA binding. Consistently, the cytotoxicity of the quercetin/Cu2+ system to endothelial cells was reduced in the HSA-diligand complex. These results demonstrate the possibility of developing serum albumin-based carriers for the protection of bioactive flavonoids in their nutritional application.

Serum albumin mitigated perfluorooctane sulfonate-induced cytotoxicity by affecting the cellular responses.

During the wide applications of perfluorinated materials such as perfluorooctane sulfonate (PFOS) in commercial and industrial products, the potential toxicity of these engineered compounds has attracted more and more attention. As a typical environmental pollutant, PFOS could preferentially bind to albumin protein in vivo. However, the role of protein-PFOS interactions in the cytotoxicity of PFOS was not stressed enough. Herein, we investigated the interactions of PFOS with human serum albumin (HSA, the most abundant protein in human plasma) using both experimental and theoretical approaches. It was demonstrated that PFOS could mainly bind to the Sudlow site I of HSA to generate HSA-PFOS complex through hydrogen bonds and van der Waals forces. Toxicity assays with endothelial cells illustrated that the binding of HSA could significantly attenuate the intracellular uptake and subcellular distribution of PFOS, thereby inhibiting the formation of reactive oxygen species and toxicity for those HSA-bound PFOS. Similarly, the presence of fetal bovine serum in the cell culture media greatly reduced PFOS-caused cytotoxicity. Conclusively, our study reveals that the binding of albumin protein to PFOS could mitigate its toxicity by the modulation of cellular responses. The formation of protein-complexed contaminants would significantly reduce the bioavailability of these chemicals and subsequently mitigate their environmental toxicology to the human health.

pH-dependent self-assembly mechanism of a single repetitive domain from a spider silk protein.

Spider silk is self-assembled from full-length silk proteins, and some silk protein fragments can also form silk-like fibers in vitro. However, the mechanism underlying the silk fiber formation is not understood well. In this study, we investigated the fiber formation of a single repetitive domain (RP) from a minor ampullate silk protein (MiSp). Our findings revealed that pH and salt concentration affect not only the stability of MiSp-RP but also its self-assembly into fibers and aggregates. Using nuclear magnetic resonance (NMR) spectroscopy, we solved the three-dimensional (3D) structure of MiSp RP in aqueous solution. On the basis of the structure and mutagenesis, we revealed that charge-dipole interactions are responsible for the pH- and salt-dependent properties of MiSp-RP. Our results indicate that fiber formation is regulated by a delicate balance between intermolecular and intramolecular interactions, rather than by the protein stability alone. These findings have implications for the design of silk proteins for mass production of spider silk.

Efficacy and Dose-Response Relationship of Stereotactic Body Radiotherapy for Abdominal Lymph Node Metastases from Hepatocellular Carcinoma.

BACKGROUND: The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Between 2010 and 2020, data of 148 patients with HCC with abdominal LNM, including 114 who underwent SBRT and 34 who received conventional fractionation radiation therapy (CFRT), were collected. A total radiation dose of 28-60 Gy was delivered in 3-30 fractions, with a median biologic effective dose (BED) of 60 Gy (range, 39-105 Gy). Freedom from local progression (FFLP) and overall survival (OS) rates were analyzed. RESULTS: With a median follow-up of 13.6 months (range, 0.4-96.0 months), the 2-year FFLP and OS rates of the entire cohort were 70.6% and 49.7%, respectively. Median OS of the SBRT group was longer than the CFRT group (29.7 vs. 9.9 months, P = .007). A dose-response relationship was observed between local control and BED in either the entire cohort or the SBRT subgroup. Patients who received SBRT with a BED ≥60 Gy had significantly higher 2-year FFLP and OS rates than those who received a BED <60 Gy (80.1% vs. 63.4%, P = .004; 68.3% vs. 33.0%, P < .001). On multivariate analysis, BED was an independent prognostic factor for both FFLP and OS. CONCLUSIONS: SBRT achieved satisfactory local control and survival with feasible toxicities in patients with HCC with abdominal LNM. Moreover, the findings of this large series suggest a dose-response relationship between local control and BED.

Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial.

BACKGROUND: Toripalimab is a PD-1 inhibitor that is approved for the treatment of advanced oesophageal squamous cell carcinoma, but its efficacy in locally advanced disease is unclear. We administered toripalimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the activity and safety of this regimen, and potential biomarkers. METHODS: EC-CRT-001 was a single-arm, phase 2 trial done at Sun Yat-sen University Cancer Center (Guangzhou, China). Patients aged 18-70 years with untreated, unresectable, stage I-IVA oesophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (50·4 Gy in 28 fractions), chemotherapy (five cycles of weekly intravenous paclitaxel [50 mg/m2] and cisplatin [25 mg/m2]), and toripalimab (240 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the complete response rate at 3 months after radiotherapy by investigator assessment. Secondary endpoints were overall survival, progression-free survival, duration of response, quality of life (not reported here), and safety. All enrolled patients were included in the activity and safety analyses. The trial is registered with ClinicalTrials.gov, NCT04005170; enrolment is completed and follow-up is ongoing. FINDINGS: Between Nov 12, 2019, and Jan 25, 2021, 42 patients were enrolled. The median age was 56 years (IQR 53-63), 39 (93%) of 42 patients had stage III or IVA disease, and 32 (76%) patients were male and 10 (24%) were female. 40 (95%) of 42 patients completed the planned chemoradiotherapy and 26 (62%; 95% CI 46-76) of 42 had a complete response. The median duration of response was 12·1 months (95% CI 5·9-18·2). After a median follow-up of 14·9 months (IQR 11·9-18·4), 1-year overall survival was 78·4% (95% CI 66·9-92·0) and 1-year progression-free survival was 54·5% (41·3-72·0). The most common grade 3 or worse adverse event was lymphopenia (36 [86%] of 42). One (2%) patient died from treatment-related pneumonitis. INTERPRETATION: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. FUNDING: National Natural Science Foundation of China and Sci-Tech Project Foundation of Guangzhou. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Binding of serum albumin to perfluorooctanoic acid reduced cytotoxicity.

With the ubiquitous applications of perfluorinated compounds such as perfluorooctanoic acid (PFOA) in industrial and commercial products, the toxicity of these engineered materials in environmental and public health is received growing attention. As a typical organic pollutant, PFOA has been extensively found in wildlife and human bodies, and can preferentially bind to serum albumin in vivo. However, the importance of protein-PFOA interactions on the cytotoxicity of PFOA could not be stressed enough. In this study, we used both experimental and theoretical approaches, to investigate the interactions of PFOA with bovine serum albumin (BSA, the most abundant protein in blood). It was found that PFOA could mainly interact with Sudlow site I of BSA to form BSA-PFOA complex, in which van der Waals forces and hydrogen bonds played dominant roles. Moreover, the strong binding of BSA could greatly alter the cellular uptake and distribution of PFOA in human endothelial cells, and result in the decreases of reactive oxygen species formation and cytotoxicity for these BSA-coated PFOA. Consistently, the addition of fetal bovine serum into cell culture medium also significantly mitigated PFOA-induced cytotoxicity, which was attributed to the extracellular complexation between PFOA and serum proteins. Altogether, our study demonstrates that the binding of serum albumin to PFOA could reduce its toxicity by affecting the cellular responses.

1.3/1.4 µm dual-wave band dissipative soliton resonance in a passively mode-locked Bi-doped phosphosilicate fiber laser.

We report the 1.3/1.4 µm dual-wave band dissipative soliton resonance (DSR) in a passively mode-locked bismuth-doped phosphosilicate fiber (Bi-PSF) laser. The low-water-peak Bi-PSF with two bismuth active centers associated with silicon and phosphorus supports the O+E-band gain. Using a 1239 nm home-made Raman fiber laser as pump source and nonlinear amplifying loop mirror for initiating mode-locking, stable DSR operation at 1343 and 1406 nm is achieved with the spectral bandwidth of 12 and 16 nm. The pulse duration with the pump power increases from 62 to 270 ps with a repetition frequency of 4.069 MHz. The average power is 11.05 mW corresponding to the maximum energy of 2.7 nJ. This is, to the best of our knowledge, the first demonstration of a mode-locked fiber laser in the ∼1.38 µm water absorption band and the O+E dual-wave band operation for applications in all-spectral-band communications, bio-medical imaging, and terahertz difference frequency generation.