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Fungal infections gradually lead to a high mortality rate due to difficulties in diagnosis, the limited number of antifungal drugs available, and the appearance of resistant isolates. Here, we developed a calcofluor white-cholesteryl hydrogen succinate conjugate (CFW-CHSc) as a novel nanomaterial that specifically binds to chitin chains in the cell wall. We showed that fluorescent-dye loaded CFW-CHSc-liposomes entered the cytoplasm of

The monodispersed NiSe hierarchical microspheres (NiSe-112) were controllably synthesized by the facile solvothermal method and employed as the high-efficiency counter electrode (CE) electrocatalysts for the triiodide (I3−) reduction reaction (IRR). The obtained NiSe-112 combines the advantages of the well monodispersity, the inimitable 3D micro/nanostructure and loosened rough surface structure, which not only facilitated the permeation of the electrolyte containing I3−/I− redox couple, but also provided the substantial active sites for the IRR. As a result, NiSe-112 exhibited excellent catalytic activity for IRR accompanying with an impressive photoelectric conversion efficiency of 7.67 %, which is compared to that of the conventional Pt-based DSSCs (7.85 %). The relevant electrochemical measurements demonstrated that the obtained NiSe-112 possessed Pt-like catalytic activity, rapid electron transport capability and excellent electrochemical stability. Therefore, three-dimensional hierarchical structural NiSe microspheres have a great potential to replace the noble metal Pt, which is beneficial to promote the development of the low-cost CE catalysts for DSSCs.

Osimertinib is a third-generation tyrosine kinase inhibitor for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-sensitizing mutations and acquired drug-resistant mutation T790M. Despite promising treatment benefits of osimertinib in first- and second-line settings, drug resistance has been an inevitable clinical issue. The resistance to osimertinib is heterogeneous, which may involve EGFR-dependent and independent mechanisms as well as histological transformation from NSCLC to small cell lung cancer (SCLC). Current clinical studies of NSCLC were mainly focused on patients with EGFR-sensitizing mutations or acquired T790M mutation or both. The treatments and drug-resistant mechanisms in patients with de-novo T790M mutation remain undefined. Herein, we reported the presence of the less common de-novo EGFR T790M mutation in a stage IV NSCLC patient. The patient received osimertinib as first-line treatment and achieved durable progression-free survival (PFS) for 24 months. After osimertinib resistance, tumor biopsy indicated histologic transformation from NSCLC to SCLC. Given persistent presence of de-novo T790M mutation, osimertinib was used in combination with etoposide and cisplatin as second-line treatment and the patient achieved partial response with PFS of 7 months. Our study suggested that NSCLC patients with de-novo T790M mutation could also benefit from osimertinib and the SCLC transformation may be a potential resistance mechanism that could be targeted through the combination of targeted therapy and chemotherapy.

Electric vehicles (EVs) are widely applied in logistics companies’ urban logistics distribution, as fuel prices increase and environmental awareness grows. This study introduces an EV charging station (CS) location-routing problem with time windows and resource sharing (EVCS-LRPTWRS). Resource sharing, among multiple depots within multiple service periods is proposed to adjust the transportation resource configuration for a sustainable logistics development. Solving the EVCS-LRPTWRS involves a periodic CS location selection and a multi-depot multi-period EV routing optimization. A bi-objective nonlinear programming model is proposed to formulate the EVCS-LRPTWRS with a minimum total operating cost and number of EVs. A hybrid algorithm combining the Gaussian mixture clustering algorithm (GMCA) with the improved nondominated sorting genetic algorithm-II (INSGA-II) is designed to address the EVCS-LRPTWRS. The GMCA is employed to assign customers to appropriate depots in various service periods in order to reduce the computational complexity. The INSGA-II is adopted to obtain the Pareto optimal solutions by using the CS insertion operation to select CS locations and integrating the elite retention mechanism to ensure a stable and excellent performance. The superiority of the hybrid algorithm is proven by comparison with the other three algorithms (i.e., multi-objective genetic algorithm, multi-objective particle swarm optimization, and multi-objective ant colony optimization). An empirical study of the EVCS-LRPTWRS in Chongqing City, China is conducted. Then, four types of service period divisions and three scenarios of resource sharing modes are further analyzed and discussed. The empirical results demonstrate the validity and practicability of the proposed solution method in realizing a sustainable operation in EV distribution networks.

Objective: This phase 3 study aimed to test equivalence in efficacy and safety for QL1101, a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab, 15 mg/kg every 3-week for 6 cycles. This was followed by maintenance treatment with single agent QL1101 every 3-week. The primary end-point was objective response rate (ORR), with secondary end-points being progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Results: Of 675 patients, 535 eligible patients were randomized to the QL1101 group (n = 269) and bevacizumab group (n = 266). ORRs were 52.8% and 56.8%, respectively, for the QL1101 and bevacizumab groups, with an ORR hazard ratio 0.93 (95% confidence interval: 0.8–0131.1). The PFS, OS, DCR, and AEs were comparable between the 2 groups, which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history. Conclusions: QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

The occurrence of NH3-SCR (selective catalytic reduction of NO with NH3) reaction on catalyst surface typically requires acid and redox sites. However, the role of acid-redox interaction on NH3-SCR performance is still obscure due to complex acidities and entangled acid-redox sites. Herein, three types of model Ce2(SO4)3-CeO2 catalysts with distinct interfaces are constructed to reveal the effect of acid-redox interaction on NH3-SCR performance. That is, SO42-/CeO2-VS (vapor sulfation of ceria) with strong acid-redox interfacial contact, SO42-/CeO2-WI (wet impregnation), and SO42-/CeO2-SG (solid grinding) with limited interfaces. It is found the redox property is significantly disturbed as a result of the electron-withdrawing effect from the sulfate. Theoretical result unravels that the introduction of Ce2(SO4)3 retards the oxygen vacancy formation over CeO2. Due to restricted interfaces in SO42-/CeO2-SG, the negative influence from acid sites is greatly alleviated. Further mechanism study discloses the weakened acid-redox interaction actually changes the nature of surface NOx species, resulting in the generation of reactive species (*O-N-O* and cis-N2O22-) and the promotion of surface reaction via Langmuir-Hinshelwood (L-H) mechanism.

Background There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression‐free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score. Methods This was a post hoc analysis of a multicenter, double‐blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively. Results The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5–11.0) versus 3.2 (95% CI: 1.2–5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2–0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0–11.0) vs. 4.8 (95% CI: 1.2–8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses. Conclusions The occurrence of hypertension might be a clinical indicator predicting the efficacy of third‐line anlotinib treatment in patients with SCC., In SCC patients who received third‐line anlotinib treatment, the median PFS was longer in patients who developed hypertension than in those who did not. Our results suggest that the occurrence of hypertension during treatment might be a clinical indicator predicting the efficacy of third‐line anlotinib in patients with SCC.

Background Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. Materials and Methods This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1–14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. Results A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4–4.5) over placebo group (1.5 months; 95% CI, 1.4–1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27–0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8–9.7 vs. 7.2 months; 95% CI, 6.2–8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). Conclusion Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. Implications for Practice In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.

Harsh environments, which are complex, mutable, and hard to model, prevent high-accuracy positioning and navigation. In this article, a novel magnetic-based positioning system (MBPS) based on a low-frequency time-varying magnetic field (MF) is reported. Related investigations have shown that low-frequency MF signals have better propagation characteristics in harsh environments and achieve good penetration into obstacles. Unlike the intensity decay method, our proposed method is not affected by the uncertainty of the intensity decay model caused by the complex magnetic medium. The novelty of our proposed approach lies in the large effective coverage, outstanding penetrability, and rapid results offered by it compared with those of the traditional method, achieved using a constant magnetic feature vector as the observation. Furthermore, considering the installation error of the magnetic beacon (MB), which is hard to avoid and measure, we proposed an improved Rao–Blackwellized particle filter (RBPF) algorithm to estimate the receiver position and installing error on the position and angle. For the proposed MBPS, the best accuracy of 0.06 m can be reached under conditions at which the installing position error is 0.5 m and the angle error is 10°–15° with daily electromagnetic interference. The MB and its model verification were also investigated. In summary, the effectiveness of the proposed MBPS and the algorithm was verified sufficiently in this study.

There is a strong demand for Planetary Exploration Mobile robots (PEMRs) that have the capability of the traversability, stability, efficiency and high load while tackling the specialized tasks on planet surface. In this paper, an electric parallel wheel-legged hexapod robot which has high-adaption locomotion on the unstructured terrain is presented. Also, the hybrid control framework, which enables robot to stably carry the heavy loads as well as to traverse the uneven terrain by utilizing both legged and wheeled locomotion, is also proposed. Based on this framework, robot controls the multiple DOF leg for performing high-adaption locomotion to negotiate obstacles via Gait Generator (GG). Additionally, by using Whole-Body Control (WBC) of framework, robot has the capability of flexibly accommodating the uneven terrain by Attitude Control (AC) kinematically adjusting the length of legs like an active suspension system, and by Force/torque Balance Control (FBC) equally distributing the Ground Reaction Force (GRF) to maintain a stable body. The simulation and experiment are employed to validate the proposed framework with the physical system in the planetary analog environments. Particularly, to smoothly demonstrate the performance of robot transporting heavy loads, the experiment of carrying 3-person load of about 240 kg is deployed.

Research about the functionalized covalent organic framework (COF) materials with well hydrophilic characteristics is significant on account of their application in the removal of dyes in wastewater. In this work, two anionic COF materials (TFPB-Pa-SO3H COF and TFPB-BDSA COF) were successfully synthesized with sulfonated modification as dyestuffs sorbent to be used in the adsorption of cationic dyes. Two prepared COF materials exhibited predominant hydrophilicity with lower water contact angles (35° and 27°) compared with reported COF materials. The sulfonated groups on COFs can efficiently adsorb cationic dyes through electrostatic interaction, which can moderately ameliorate the adsorptive capacity towards hydro soluble dyes. TFPB-Pa-SO3H COF and TFPB-BDSA COF showed superfast adsorption equilibrium to MLB (1 and 2 min) and the higher adsorption uptakes of CV (1559 and 1288 mg g−1), which manifested that the adsorption rate may be closely related to the solubilities of host COFs materials as well as guest dye molecule in aqueous solution; while the adsorption stability between COFs materials and the dye molecule adsorbed on the COFs skeleton accounted for the highly effective adsorption of the aim dye in large quantity. In addition, two COFs as adsorbing materials were successfully applied to the removal of dyes molecules in real water samples.

This paper provides a legged stable walking control strategy based on multi-sensor information feedback about BIT-NAZA-II, a large load parallel hexapod wheel-legged robot developing for the problem of vertical contact impact and horizontal sliding of heavy leg robot in complex terrain environments. The BIT-NAZA-II robot has six legs and six wheels, and the wheels are installed on the foot-end. The wheels of each foot-end for the legs of the robot are locked when walking with legs. In order to realize the smooth transition between swing phase and stance phase, the leg motion is divided into different stages for control by state machine switching controller based on event (SMSCE). In the Z-direction, in order to avoid the shaking of the body caused by the contact impact at the moment of contact between the foot-end and the ground during the walking of the robot, an active compliance controller (ACC) based on impedance control (IC) is applied to solve the problem of contact impact. Moreover, in the X-direction, the swing leg retraction (SLR) based on Bezier curve (BC) is introduced to generate the foot-end trajectory of the robot, which solves the slip problem of the heavy leg robot and improves the horizontal stability. Finally, the control strategy of stable walking is respectively verified by the simulations and experiments. The results show that the ACC based on IC can effectively reduce the contact impact between the foot-end and the ground in the Z-direction and improve the stability of body. Besides, the anti-sliding ability is realized after introducing SLR based on BC in the X-direction, and we also verify that stable walking control strategy is effective, which provides a reference value for the stable walking of heavy leg robot in complex terrain.

Background: Epidemiologic studies have shown that persons suffering from psychotic disorders are at increased risk of violent behavior. Several factors have been shown to predict violent behavior among persons with psychosis. However, prior research is limited in that these factors have not been explored simultaneously within the same study. Methods: The current study, therefore, aimed to determine which demographic, clinical, cognitive, and developmental characteristics were associated with an increased likelihood of violence among patients diagnosed with a psychotic disorder and which combination of these best predicted a history of violence. Participants (n=53) completed measures of demographics, violence risk, psychotic and personality symptoms, trauma, psychopathy and cognitive functioning. Results: Bivariate relationships were conducted to compare the history of violent behavior between all variables. Additionally, a binary logistic regression was run predicting participants’ history of violence. Several demographic, cognitive, clinical, and developmental factors were associated with increased odds of having a history of violence. The overall correct classification rate for the model was 92.2%, with 87.5% of participants without a history of violence and 91.4% with a history of violence being correctly classified. The model included antisocial personality traits, poor behavioral controls, head injury, not accepting responsibility, lacking goals, prior supervision failures, and HCR-20 total score. Conclusion: The binary logistic regression model showed good accuracy in predicting a history of violence in persons with psychosis. These findings are consistent with prior research and can inform efforts at risk assessment and identification of treatment targets for people with a psychotic disorder who are at highest risk of violence.

Summary Background Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs. Methods SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov , NCT02588170 . Follow-up is ongoing. Findings Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1–16·7) in the surufatinib group and 16·6 months (9·2–not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4–11·1) in the surufatinib group versus 3·8 months (3·7–5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22–0·50; p Interpretation Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population. Funding Hutchison MediPharma.

Molybdenum phosphide is one of the most potential electrocatalysts for the hydrogen evolution reaction (HER), whereas it is still challenging to achieve an efficient molybdenum phosphide-based catalyst that performs well over a wide pH range. Herein, a porous nanoplate composed of small MoP flakes confined in thin N, P, S-triple-doped carbon (MoP@NPSC) was prepared by the assembly of phosphomolybdic acid (H3PMo12O40·nH2O, {PMo12}) and egg white, followed by phosphorization. Given its small size (ca. 1 nm) in favor of deriving small particles and the oxygen-rich surface with strong coordination ability, the {PMo12} cluster was selected to combine with egg white to obtain a lamellar hybrid precursor via a hydrogen bond. Through controllable phosphating, a nanoplate organized by interconnected MoP particles was generated, accompanied by the in situ formation of the N, P, S-doped carbon thin layer and pores from the pyrolysis of egg white. The plentiful pores, thin carbon coating, and multielement doping bring about promoted electrolyte/bubble diffusion, enhanced conductivity and stability, and lowered adsorption energy of hydrogen/hydroxyl, respectively. All of the above merits endow MoP@NPSC with prominent activity with low overpotentials of 50, 76, and 71 mV at 10 mA cm-2 toward the HER in alkaline, neutral, and acid media, respectively, and nearly no attenuation after 40 h of testing. Especially, compared with commercial Pt/C, MoP@NPSC exhibits similar low onset potential and even better at large current density in 1 M KOH. The electrolyzer equipped with the MoP@NPSC cathode and the NiFe-LDH anode requires only 1.52 V to deliver 10 mA cm-2 and can be powered by a solar cell (1.524 V) charged by sunlight.

Sn-based electrocatalysts have been gaining increasing attention due to their potential contribution in the conversion of CO2 into HCOOH driven by sustainable energy sources; however, their actual capability to catalyze CO2 reduction reaction (CO2RR) still cannot meet the requirements of commercial-scale applications. Therefore developing Sn-based catalyst is of vital importance. Herein, the sheet-like heterophase SnO2/Sn3O4 with a high density of phase interfaces has been first engineered by a facile hydrothermal process, with Sn3O4 as the dominant phase. The evidences from experiments and theoretical simulation indicate that the charge redistribution and built-in electric field at heterophase interfaces boost CO2 adsorption and HCOO* formation, accelerate the charge transfer between the catalysts and reactants, and ultimately greatly elevate the intrinsic activity of the heterophase SnO2/Sn3O4 towards CO2RR. Meanwhile, the in-situ generated porous structure and metal Sn during CO2RR improve the mass transmission within the interlayer volume and the conductivity of SnO2/Sn3O4. The heterophase SnO2/Sn3O4 displays high activity and selectivity for CO2RR, achieving an improvement in CO2 reduction current density, 88.3% Faradaic efficiency of HCOOH conversion at −0.9 VRHE, along with a long-term tolerance in CO2RR. This study demonstrates that heterophase interface engineering is an efficient strategy to regulate advanced catalysts for different applications.

Rational microstructure design of carbon based composites is becoming a promising method to reinforce their electromagnetic (EM) wave absorption performance, but their synthesis remains a challenge. Herein, we have reported a design of small-size Ni2P grown on carbon nanotubes (CNTs) as lightweight and high efficiency EM wave absorber. The Ni2P NPs can be uniformly grown on CNTs by controlling the nucleation and growth rate of Ni2P during the synthesis. The size and coverage of Ni2P on CNTs can be tuned by adjusting the reaction conditions with a high yield, which is large favorable for adjusting their application performance. The Ni2P/CNTs sample with low filler loading (30 wt%) in the paraffin wax exhibits a good wave absorption performance with the minimum reflection loss (RL mini) value of −51.8 dB at 5.28 GHz. Moreover, it shows a good EM wave absorption ability even at the thinnest thickness of 2 mm (−46.1 dB), and an effective absorption bandwidth of 11.68 GHz is achieved when the absorber thickness is in the range of 1.5–5 mm. The excellent EM wave absorbing performance makes the Ni2P/CNTs as a promising new microwave absorbing material in sustainable filed.

Background Anlotinib showed significant survival benefits in advanced non‐small cell lung cancer (NSCLC) patients as a third‐ or further‐line treatment in the ALTER0303 trial. We aimed to evaluate the efficacy of anlotinib in patients with different histologies. Methods The ALTER0303 trial was a randomized, open‐label, phase 3 study of anlotinib in NSCLC patients previously treated with at least two lines of chemotherapy or a tyrosine kinase inhibitor (TKI) in 31 centers in China. Patients were randomly assigned at a 2:1 ratio to receive anlotinib (12 mg QD from days 1 to 14 of a 21‐day cycle) or placebo until progression or intolerable toxicity. The primary endpoint was overall survival (OS). We assessed the efficacy of anlotinib in histological subgroups in the full analysis set. Results In the ALTER0303 trial, 336 patients had the histological subtype of adenocarcinoma (ACC), 86 patients had the histological subtype of squamous cell carcinoma (SCC), and 15 patients had another subtype. In the ACC subgroup, the median OS time was significantly improved with anlotinib compared with placebo (9.6 months vs 6.9 months, P = .0051), as was the median progression‐free survival (PFS) time (5.5 months vs 1.4 months, P, In this study, we evaluated the efficacy of anlotinib as third‐ or further‐line treatment for patient with different histological types of NSCLC. In the ALTER0303 trial, 336 patients had the histological subtype of adenocarcinoma (ACC), 86 patients had the histological subtype of squamous cell carcinoma (SCC), and 15 patients had another subtype. Our findings suggest that anlotinib significantly improves PFS and OS in ACC patients and has a tendency to prolong survival in SCC patients.

Dynamic customer demands impose new challenges for vehicle routing optimization with time windows, in which customer demands appear dynamically within the working periods of depots. The delivery routes should be adjusted for the new customer demands as soon as possible when new customer demands emerge. This study investigates a collaborative multidepot vehicle routing problem with dynamic customer demands and time windows (CMVRPDCDTW) by considering resource sharing and dynamic customer demands. Resource sharing of multidepot across multiple service periods can maximize logistics resource utilization and improve the operating efficiency of delivery logistics networks. A bi-objective optimization model is constructed to optimize the vehicle routes while minimizing the total operating cost and number of vehicles. A hybrid algorithm composed of the improved k-medoids clustering algorithm and improved multiobjective particle swarm optimization based on the dynamic insertion strategy (IMOPSO-DIS) algorithm is designed to find near-optimal solutions for the proposed problem. The improved k-medoids clustering algorithm assigns customers to depots in terms of specific distances to obtain the clustering units, whereas the IMOPSO-DIS algorithm optimizes vehicle routes for each clustering unit by updating the external archive. The elite learning strategy and dynamic insertion strategy are applied to maintain the diversity of the swarm and enhance the search ability in the dynamic environment. The experiment results with 26 instances show that the performance of IMOPSO-DIS is superior to the performance of multiobjective particle swarm optimization, nondominated sorting genetic algorithm-II, and multiobjective evolutionary algorithm. A case study in Chongqing City, China is implemented, and the related results are analyzed. This study provides efficient optimization strategies to solve CMVRPDCDTW. The results reveal a 32.5% reduction in total operating costs and savings of 29 delivery vehicles after optimization. It can also improve the intelligence level of the distribution logistics network, promote the sustainable development of urban logistics and transportation systems, and has meaningful implications for enterprises and government to provide theoretical and decision supports in economic and social development.

During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.

BACKGROUND: Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation. METHODS: The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status. RESULTS: For patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38–0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95% CI: 0.13–0.32, P

Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC.The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/mBetween Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death).Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population.Jiangsu Hengrui Pharmaceuticals.

Interactions between T follicular helper (Tfh) cells and germinal center B cells are essential for the differentiation of B cells and specific antibody responses against HIV-1 infection. However, the extent to which HIV-1 infection affects the dynamic interplay between these two cell populations in the bloodstream remains unclear. In this study, the dynamics of circulating Tfh (cTfh) and B cells and their relationship in individuals with acute and chronic HIV-1 infection were investigated. Twenty-five study subjects were enrolled from the Beijing PRIMO clinical cohort, a prospective cohort of HIV-1-negative men who have sex with men (MSM) for the identification of cases of acute HIV-1 infection (AHI) at Beijing Youan Hospital, Capital Medical University. Individuals with AHI were selected at random. Matched samples were also collected and analyzed from the same patients with chronic HIV-1 infection. None of the study subjects received antiretroviral therapy during acute or chronic infection. Multicolor flow cytometry was used for the immunophenotypic and functional characterization of cTfh cell and B cell subsets. AHI resulted in increased proportions in bulk cTfh, ICOS

To investigate the health-related quality of life (HRQoL) of patients who had neuroendocrine tumors (NETs) from SANET trials.Eligible patients were randomized in a 2:1 ratio to receive surufatinib or placebo. HRQoL questionnaires, including the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-G.I.NET21, were collected. The prespecified HRQoL outcome was the mean change of scores from baseline to the last available visit for each domain. Time until definitive deterioration (TUDD) was defined as the time from randomization to deterioration of ≥10 points from baseline in domain score, disease progression, or death.370 patients were enrolled and randomly assigned to surufatinib (n = 242) or placebo (n = 128). No significant difference in mean scores change from baseline to the last available visit was observed for QLQ-C30 and QLQ- G.I.NET21 domains, with the exception of diarrhea. The mean score of diarrhea increased 11.7 points from baseline in the surufatinib arm and decreased 1.2 points in the placebo arm, and the between-group difference was 12.9 points. Compared with placebo, surufatinib treated patients had a significantly longer TUDD for dyspnea (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.39-0.86; P = 0.0058) and a significantly shorter TUDD for diarrhea (HR 2.91; 95% CI, 1.66-5.10; P 0.0001). There were no significant differences in TUDD for the remaining domains of QLQ-C30 and G.I.NET-21.HRQoL was similar in patients treated with surufatinib and placebo except for diarrhea. The preservation of HRQoL supports surufatinib as a treatment option for NETs.ClinicalTrials.gov: NCT02589821, NCT02588170.

With the advent of the era of big data, new technologies such as cloud computing and artificial intelligence are changing with each passing day. More and more science and technology are applied to the financial field, which greatly promotes a new round of prosperity and development of China’s financial market. However, because big data has the characteristics of fast spreading speed, wide penetration area, strong concealment, and difficulty in supervision, the integration of technology and finance in the era of big data will also generate some new risk problems. Based on this, this article starts with the connotation and characteristics of financial technology, summarizes the risk performance of financial technology, and proposes corresponding countermeasures, aiming to promote the healthy and stable development of China’s financial technology.

CuO/SiO2 catalysts with a vast difference in copper dispersion were prepared by impregnation (denoted as CuSi-IM) and ammonia-evaporation (denoted as CuSi-AE) methods and tested for NO reduction by CO. Despite the inferior dispersion of copper species in the CuSi-IM catalysts, they exhibited significantly higher NO conversion efficiency, with more than one order of activity enhancement achieved in comparison with the CuSi-AE samples. Ex situ XRD, in situ DRIFTS, and CO-TPR characterization were carried out to study the nature of active copper species and their evolution under reaction conditions. A clear dispersion-dependent reduction behavior (for CuSi-AE, step-wise reduction; for CuSi-IM, one step reduction) under a CO atmosphere was observed, and the generation of Cu0 preferentially occurred at lower temperatures for the CuSi-IM samples, which accounted for the better performance in the NO + CO reaction. Lastly, NO-TPD and TPSR experiments were performed and the essential role of Cu0 in promoting NO dissociation was proposed. The results of the present study would deepen our understanding on the reaction behaviors of copper catalysts in the NO + CO reaction.

The development of low-cost, environmental friendliness, outstanding catalytic activity, superior conductivity and good stability counter electrode (CE) catalyst in dye-sensitized solar cells (DSSCs) is important to promote the commercial application of DSSCs. Here, WN/nitrogen-doped reduced graphite oxide hybrids (WN/NrGO) had been synthesized by hydrothermal method followed by nitridation treatment, which used as CE catalysts for catalyzing I3− to I−. The combined WN and nitrogen-doped reduced graphite oxide (NrGO) into WN/NrGO could effectively regulate the catalytic activity for the reduction of I3−, accelerate the charge transfer at the interface, and then the synergistic effect between of them can be fully achieved. When the WN/NrGO served as the CE catalyst in DSSCs, the photoelectric conversion efficiency (PCE) of 7.42% has been obtained, compared to the conventional Pt-based DSSCs (7.71%). Meanwhile, as-prepared WN/NrGO exhibited higher PCE than that of the solo WN (6.19%) and NrGO (5.81%) in parallel. A series of electrochemical measures revealed that the WN/NrGO displayed the higher catalytic activity and charge transfer ability than that of the solo WN and NrGO, so the synthesized low-cost WN/NrGO have an potential to be used as the effectively CE catalysts for the replacement of the noble Pt.

NO reduction by CO was investigated over CO-pretreated CuO/MnOx/γ-Al2O3 catalysts with different metal precursors (nitrate and acetate). It was found that the catalyst prepared from acetate salts (Cu/Mn/Al-A) exhibited significantly higher activity than counterpart catalyst from nitrate precursors (Cu/Mn/Al-N). XRD, XPS and in situ DRIFT were carried out to approach the nature for the different catalytic performance. For both catalysts, copper mainly existed as CuO, but the status of manganese oxide was markedly different. Mn(IV) was predominant in Cu/Mn/Al-N and Mn(III) was enriched in Cu/Mn/Al-A. As a result, different dispersion behaviors of manganese oxide on γ-Al2O3 were displayed, which induced inconsistent Cu-Mn contact. The catalyst obtained from acetate precursor exhibited enriched Cu-Mn contact and thus more Cu+-□-Mn3+/2+ entities would be produced after CO pretreatment, leading to promoted NO dissociation and favorable performance in NO reduction by CO. The present study sheds light on the effective tuning of Cu-O-Mn interfacial sites in CuO/MnOx/γ-Al2O3 via modulating the dispersion behaviors of surface components.

The counter electrode material of dye-sensitized solar cells (DSSCs) with excellent catalytic activity and fast electron transfer ability could effectively improve the overall photoelectrical conversion efficiency (PCE). In this work, monodispersed Co9S8 nanocrystals (NCs) were in situ grown on the surface of the reduced graphene oxide (RGO) through a simple hot-injection method. Due to the confinement of organic ligand oleylamine, the Co9S8 NCs with the size of ca. 8 nm were mainly dispersed on the surface of RGO (Co9S8/RGO). The Co9S8/RGO composite with the optimal contents (RGO contents of 44.4 wt%) was prepared by controlling the amount of graphene oxide (GO) added, which possessed the optimal catalytic active site numbers and electron transfer ability as it showed a higher PCE of 7.31%. It was higher than that of the solo Co9S8 NCs and comparable to that of the Pt (7.72%). The electrochemical characteristics (cyclic voltammetry, Tafel polarization curve, and electrochemical impedance spectroscopy) confirmed their excellent electrocatalytic activity towards I3−/I− redox reduction. Furthermore, the calculations based on the density functional theory (DFT) revealed that the absorption energy of I3− on the Co site at the interface of Co9S8/RGO composite was −1.881 eV, which was higher than that of solo Co9S8 NCs (−1.078 eV). So, Co atoms in the Co9S8/RGO interface was the predominant catalytic active center for the I3− reduction. This in situ growth strategy provided a new strategy for the preparation of electrocatalytic materials.

SnS, composed of earth abundant and environmentally benign elements, is a unique material for wide applications in thermoelectricity, solar energy conversion, photocatalysis, and electrochemical en...

Electrochemical conversion of CO2 into syngas, which can be used directly in the classical petroleum industrial processes, provides a powerful approach for achieving the recycling of anthropogenic carbon. Pd has previously been reported to be capable of converting CO2 into syngas with various CO/H2 ratios, but only at limited applied potential, which is mainly attributed to fewer active sites exposed toward electrocatalysis. Herein, high-performance Pd nanomeshes (NMs) assembled with branch-like Pd nanoparticles were designed and synthesized by using a simple interface-induced self-assembly strategy; these NMs could catalyze CO2 -into-syngas conversion with a high current density in a wide applied potential range from -0.5 to -1.0 V (vs. reversible hydrogen electrode). Further evidence validated that the enhanced activity of the Pd NMs was not only caused by the crosslinked network structure accelerating electron transport, but also by the greater number of edge and/or corner active sites exposed on the surface of the NMs, which facilitated CO2 adsorption, CO2.- formation, COOH* stabilization, and CO generation. Under optimal operating conditions, Pd NMs could balance two competing reactions: CO2 reduction and hydrogen evolution. The resultant syngases with the ideal and tunable CO/H2 ratio between 0.5:1 and 1:1 could be used directly for methanol synthesis and Fischer-Tropsch reactions.

The design of the electrode with high-area and mass capacitance is important for the practical application of supercapacitors. Here, we fabricated the porous NiCoP nanowalls supported by Ni foam (NiCo-P/NF) for supercapacitors with win-win high-area and mass capacitance. The NiCoOH nanowall precursor was prepared by controlling the deposition rate of Ni2+ and Co2+ on NF through a sodium acetate-assisted (floride-free) process. After the phosphorization, the NiCo-P nanowalls formed with high loading about 8.6 mg cm−2 on NF. The electrode combined several advantages favorable for energy storage: the plentiful pores beneficial for ion transport, the nanowalls for easy accommodation of electrolyte, good conductivity of NiCo-P for easy transport of electrons. As expected, the NiCo-P/NF exhibited a high specific mass capacitance (1,861 F g−1 at 1 A g−1, 1,070 F g−1 at 10 A g−1), and high area capacitance (17.31 F cm−2 at 5 mA cm−2 and 10 F cm−2 at 100 mA cm−2). The asymmetric supercapacitor (ASC) composed of NiCo-P/NF positive electrode coupled with commercial active carbon negative electrode exhibited a high energy density of 44.9 W h kg−1 at a power density of 750 W kg−1. The ASC can easily drive fans, electronic watch and LED lamps, implying their potential for the practical application.

Background Anlotinib is a tyrosine kinase inhibitor inhibiting angiogenesis. This multicenter, randomized phase II trial aimed to investigate the efficacy and safety of anlotinib in comparison with sunitinib as first-line treatment for patients with metastatic renal cell carcinoma (mRCC). Materials and Methods Patients with mRCC from 13 clinical centers were randomly assigned in a 2:1 ratio to receive anlotinib (n = 90) or sunitinib (n = 43). Anlotinib was given orally at a dose of 12 mg once daily (2 weeks on/1 week off), and sunitinib was given orally at 50 mg once daily (4 weeks on/2 weeks off). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results The median PFS was similar with anlotinib and sunitinib (17.5 vs. 16.6 months, p > .05). The median OS (30.9 vs. 30.5 months, p > .05), ORR (30.3% vs. 27.9%), and 6-week DCR (97.8% vs. 93.0%) were similar in the two groups. Adverse events (AEs) of grade 3 or 4 were significantly less frequent with anlotinib than with sunitinib (28.9% vs. 55.8%, p Conclusion The clinical efficacy of anlotinib was similar to that of sunitinib as the first-line treatment for mRCC, but with a more favorable safety profile.

Antiangiogenic therapy is a potential strategy against advanced refractory soft tissue sarcoma (STS). This retrospective study aimed to assess the efficacy and safety of apatinib in patients with advanced refractory STS and explore its clinical effect on the different histologic subtypes.Patients with pathologically diagnosed and metastatic STS who had failed at least standard chemotherapy and were naive to angiogenesis inhibitors were enrolled in this multicenter respective study. Apatinib was administered orally at a dosage of 250 to 850 mg/day. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). The secondary endpoints were progression free survival (PFS) and overall survival (OS). Tumor assessment was done after the first 4 weeks and every 8 weeks thereafter.Twenty-six patients were enrolled from seven centers between December 2015 and December 2020, consisting of 9 leiomyosarcomas (LMS), 4 rhabdomyosarcomas (RMS), 3 undifferentiated pleomorphic cell sarcomas (UPS), 3 fibrosarcomas (FS), 3 alveolar soft part sarcomas (ASPS), 2 angiosarcomas (AS) and 2 synovial sarcomas (SS). The median age was 49.0 [26-77] years, 15 females and 11 males. The ORR was 34.62% [9/26, 95% confidence interval (CI): 19.42-53.78%] and DCR was as high as 84.62% (22/26, 95% CI: 66.47-93.85%). The median progression-free survival and overall survival were 6.0 months (95% CI: 2.42-9.58) and 19.3 months (95% CI: 7.31-31.29) respectively. Furthermore, 181 patients from seven studies as well as this trial were included for pooled analysis of apatinib efficacy dependency on histology. In terms of ORR, RMS (41.7%), ASPS (78.6%), and Ewing sarcoma (40.7%) seemed to benefit more than the other histologic subtypes. Common adverse events (AEs) included hand-foot skin reaction (n=13, 50.0%), hypertension (n=12, 46.15%), proteinuria (n=10, 38.46%). Seven patients (7/26, 26.92%) had grade 3 AEs and no grade 4 AEs occurred. 2 patients (2/26, 7.69%) and 15 patients (15/26, 57.69%) experienced dose withdrawal and dose reduction respectively.Apatinib showed promising efficacy and a manageable safety profile in patients with advanced refractory STS. In addition, the response to apatinib in STS seemed to be dependent on histology.

A growing number of regimens have been approved as first-line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer. However, the optimal regimen has not been determined, especially for patients with different clinicopathological characteristics. Therefore, we performed this meta-analysis to compare the efficacy and safety of first-line treatments for patients with EGFR-mutated NSCLC based on clinicopathological characteristics, thereby providing evidence for individual patient clinical decision-making.The PubMed, Embase, Cochrane Library databases, and abstracts of ASCO, ESMO, and WCLC were searched from inception to 3 June 2021 to identify eligible randomized controlled trials (RCTs). The outcomes of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) were compared and ranked based on various clinicopathological characteristics among 14 regimens by network meta-analysis (NMA) and the surface under the cumulative ranking curve (SUCRA), respectively.25 RCTs were included, with a total of 6965 patients and 14 treatment regimens. The primary endpoint of all RCTs was PFS, and OS, ORR, and ≥3AEs were secondary endpoints. Regarding overall patients, the most distinct PFS benefit was observed in osimertinib (OSI), with the fewest ≥3AEs, whereas gefitinib plus pemetrexed-based chemotherapy (GEF+PB) provided the greatest benefit for OS. When considering EGFR mutation type, aumolertinib (AUM) and GEF+PB could be the optimal regimens in terms of PFS for patients with EGFR 19DEL and EGFR 21L858R, respectively. Notably, the efficacy of the 14 regimens for PFS varied across clinicopathological characteristics, with GEP+PB ranking first in Eastern Cooperative Oncology Group performance status (ECOG PS)= 1, Asian, age＜65 and smoking subgroups, with AUM ranking first in ECOG PS= 0 and female subgroups, with ICO+PB ranking first in age ≥65 and no smoking subgroups, and with AFA+CET ranking first in the male subgroup. In terms of brain metastases, third-generation EGFR-TKI showed obvious superiority, with AUM and OSI optimally prolonging PFS in patients with and without brain metastases, respectively. In addition, GEF+PB is a superior alternative, ranking second in terms of PFS regardless of the presence of brain metastases.OSI and GEF+PB were the most two effective first-line regimens for overall patients, ranking first in PFS and OS, respectively. GEF+PB ranked first in terms of PFS in subgroups of EGFR 21L858R, ECOG PS= 1, Asian, age65, and smoking. Meanwhile, AUM in subgroups of EGFR 19DEL, ECOG PS= 0, female, brain metastasis, OSI in the subgroup of without brain metastasis, ICO+PB in no smoking subgroup, and AFA+CET in male subgroup were the best options as for their evident superiority in PFS.

Increasing evidence indicates that neutrophil-associated prognostic markers, such as, tumor-associated neutrophils (TANs), neutrophil-to-T cell ratio (NTR) and neutrophil-to-lymphocyte ratio (NLR), are strongly correlated with the survival of patients with non-small cell lung cancer (NSCLC). However, either the association or the difference in their predictive efficacies remains unknown. To this aim, we investigated the influence of intratumoural TANs and peripheral NLR on the clinical outcome of NSCLC patients using tumor tissues, peripheral blood indexes, and clinicopathological data of 133 patients diagnosed with NSCLC. Additionally, Kendall correlation analysis was performed to identify the association between TANs and NLR. Our results revealed that intratumoural TANs were effective prognostic factors for favorable overall survival (OS), but were not associated with disease-free survival (DFS) in the subgroup analysis of 84 postoperative patients and progression-free survival (PFS) in 49 non-resectable NSCLC patients. Elevated NTR also indicated favorable prognosis, with high intratumoural NTR being correlated with prolonged OS and high stromal NTR being correlated with prolonged DFS. In contrast, peripheral NLR predicted dismal OS and DFS of patients receiving curative surgery. Furthermore, neither intratumoural nor stromal TANs were found to be associated with NLR, indicating that they were independent inflammatory indexes in predicting the prognosis of NSCLC. In conclusion, we discovered that TANs and NLR independently and oppositely predicted the clinical outcome of NSCLC patients, providing new sights on the role of neutrophil in tumor biology and survival prediction.

Malate as an important intermediate metabolite, its subcellular location, and concentration have a significant impact on fungal lipid metabolism. Previous studies showed that the mitochondrial malate transporter plays an important role in lipid accumulation in