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Renal cell carcinoma (RCC) is one of the deadliest malignant tumors. Despite significant advances in RCC treatment over the past decade, complete remission is rarely achieved. Consequently, there is an urgent need to explore and develop new therapies to improve the survival rates and quality of life for patients. In recent years, the development of tumor organoid technology has attracted widespread attention as it can more accurately simulate the spatial structure and physiological characteristics of tumors within the human body. In this review, we summarize the main methods currently used to construct kidney cancer organoids, as well as their various biological and clinical applications. Furthermore, combining organoids with other technologies, such as co-culture techniques and microfluidic technologies, can further develop organoids and address their limitations, creating more practical models. This approach summarizes the interactions between different tissues or organs during tumor progression. Finally, we also provide an outlook on the construction and application of kidney cancer organoids. These rapidly evolving kidney cancer organoids may soon become a focal point in the development of in vitro clinical models and therapeutic research for kidney cancer.

Abstract The formation of charge density waves is a long-standing open problem, particularly in dimensions higher than one. Various observations in the vanadium antimonides discovered recently further underpin this notion. Here, we study the Kagome metal CsV3Sb5 using polarized inelastic light scattering and density functional theory calculations. We observe a significant gap anisotropy with $$2{\Delta }_{\max }/{k}_{{{{{{{{\rm{B}}}}}}}}}{T}_{{{{{{{{\rm{CDW}}}}}}}}}\, \approx \, 20$$ 2 Δ max / k B T CDW ≈ 20 , far beyond the prediction of mean-field theory. The analysis of the A 1g and E 2g phonons, including those emerging below T CDW, indicates strong phonon-phonon coupling, presumably mediated by a strong electron-phonon interaction. Similarly, the asymmetric Fano-type lineshape of the A 1g amplitude mode suggests strong electron-phonon coupling below T CDW. The large electronic gap, the enhanced anharmonic phonon-phonon coupling, and the Fano shape of the amplitude mode combined are more supportive of a strong-coupling phonon-driven charge density wave transition than of a Fermi surface instability or an exotic mechanism in CsV3Sb5.

Although methods in diagnosis and therapy of hepatocellular carcinoma (HCC) have made significant progress in the past decades, the overall survival (OS) of liver cancer is still disappointing. Machine learning models have several advantages over traditional cox models in prognostic prediction. This study aimed at designing an optimal panel and constructing an optimal machine learning model in predicting prognosis for HCC. A total of 941 HCC patients with completed survival data and preoperative clinical chemistry and immunology indicators from two medical centers were included. The OCC panel was designed by univariate and multivariate cox regression analysis. Subsequently, cox model and machine-learning models were established and assessed for predicting OS and PFS in discovery cohort and internal validation cohort. The best OCC model was validated in the external validation cohort and analyzed in different subgroups. In discovery, internal and external validation cohort, C-indexes of our optimal OCC model were 0.871 (95% CI, 0.863–0.878), 0.692 (95% CI, 0.667–0.717) and 0.648 (95% CI, 0.630–0.667), respectively; the 2-year AUCs of OCC model were 0.939 (95% CI, 0.920–0.959), 0.738 (95% CI, 0.667–0.809) and 0.725 (95% CI, 0.643–0.808), respectively. For subgroup analysis of HCC patients with HBV, aged less than 65, cirrhosis or resection as first therapy, C-indexes of our optimal OCC model were 0.772 (95% CI, 0.752–0.792), 0.769 (95% CI, 0.750–0.789), 0.855 (95% CI, 0.846–0.864) and 0.760 (95% CI, 0.741–0.778), respectively. In general, the optimal OCC model based on RSF algorithm shows prognostic guidance value in HCC patients undergoing individualized treatment.

In the competitive energy market, energy retailers are facing the uncertainties of both energy price and demand, which requires them to formulate reasonable energy purchasing and selling strategies for improving their competitiveness in this market. Particularly, the attractive multi-energy retail packages are the key for retailers to increase their benefit. Therefore, combined with incentive means and price signals, five types of multi-energy retail packages such as peak-valley time-of-use (TOU) price package and day-night bundled price package are designed in this paper for retailers. The iterative interactions between retailers and end-users are modeled using a bi-level model of stochastic optimization based on multi-leader multi-follower (MLMF) Stackelberg game, in which retailers are leaders and end-users are followers. Retailers make decisions to maximize the profit considering the conditional value at risk (CVaR) while end-users optimize the satisfaction of both energy comfort and economy. Besides, a distributed algorithm is proposed to obtain the Nash equilibrium of above MLMF Stackelberg game model while the particle swarm optimization (PSO) algorithm and CPLEX solver are applied to solve the optimization model for each participant (retailer or end-user). Numeral results show that the designed retail packages can increase the overall profit of retailers, and the overall satisfaction of industrial users is the highest while that of residential users is the lowest after game interaction.

Abstract With the deregulation of electricity market in distribution systems, renewable distributed generations (RDG) are being invested in by third-party social capital, such as distributed generations operators (DGOs) and load aggregators (LAs). However, their arbitrary RDG investment and electricity trading behavior can bring great challenges to distribution system planning. In this paper, to reduce distribution system investment, a distribution system expansion planning model based on a bi-level Stackelberg game is proposed for the distribution system operator (DSO) to guide this social capital to make suitable RDG investment. In the proposed model, DSO is the leader, while DGOs and LAs are the followers. In the upper level, the DSO determines the expansion planning scheme including investments in substations and lines, and optimizes the variables provided for followers, such as RDG locations and contract prices. In the lower level, DGOs determine the RDG capacity and electricity trading strategy based on the RDG locations and contract prices, while LAs determine the RDG capacity, demand response and electricity trading strategy based on contract prices. The capacity information of the DRG is sent to the DSO for decision-making on expansion planning. To reduce the cost and risk of multiple agents, two long-term renewable energy contracts are introduced for the electricity trading. Conditional value-at-risk method is used to quantify the RDG investment risk of DGOs and LAs with different risk preferences. The effectiveness of the proposed model and method is verified by studies using the Portugal 54-bus system.

Although Mollisols are renowned for their fertility and high-productivity, high carbon (C) losses pose a substantial challenge to the sustainable provision of ecosystem services, including food security and climate regulation. Protecting these soils with a specific focus on revitalizing their C sequestration potential emerges as a crucial measure to address various threats associated with climate change. In this study, we employed a modeling approach to assess the impact of different fertilization strategies on crop yield, soil organic carbon (SOC) stock, and C sequestration efficiency (CSE) under various climate change scenarios (baseline, RCP 2.6, RCP 4.5, and RCP 8.5). The process-based SPACSYS model was calibrated and validated using data from two representative Mollisol long-term experiments in Northeast China, including three crops (wheat, maize and soyabean) and four fertilizations (no-fertilizer (CK), mineral nitrogen, phosphorus and potassium (NPK), manure only (M), and chemical fertilizers plus M (NPKM or NM)). SPACSYS effectively simulated crop yields and the dynamics of SOC stock. According to SPACSYS projections, climate change, especially the increased temperature, is anticipated to reduce maize yield by an average of 14.5% in Harbin and 13.3% in Gongzhuling, and soybean yield by an average of 10.6%, across all the treatments and climatic scenarios. Conversely, a slight but not statistically significant average yield increase of 2.5% was predicted for spring wheat. SOC stock showed a decrease of 8.2% for Harbin and 7.6% for Gonghzuling by 2,100 under the RCP scenarios. Future climates also led to a reduction in CSE by an average of 6.0% in Harbin (except NPK) and 13.4% in Gongzhuling. In addition, the higher average crop yields, annual SOC stocks, and annual CSE (10.15–15.16%) were found when manure amendments were performed under all climate scenarios compared with the chemical fertilization. Soil CSE displayed an exponential decrease with the C accumulated input, asymptotically approaching a constant. Importantly, the CSE asymptote associated with manure application was higher than that of other treatments. Our findings emphasize the consequences of climate change on crop yields, SOC stock, and CSE in the Mollisol regions, identifying manure application as a targeted fertilizer practice for effective climate change mitigation.

This paper is devoted to the synchronization of stochastic differential equations driven by the linear multiplicative fractional Brownian motion with Hurst parameter H∈(12,1). We use equivalent transformations to prove that the differential equation has a unique stationary solution, which generates a random dynamical system. Moreover, the system has the pathwise singleton set random attractor. We then establish the synchronization of the coupled differential equations and provide numerical simulation results. At the end, we discuss two specific noise forms and present the corresponding synchronization results.

With more and more agricultural parks are integrated to the electrical distribution network, the disordered characteristics of farmers’ irrigation water consumption will not only increase the cost of water and electricity, but also cause security problems in traditional term of rural distribution network, such as large short-term load fluctuation, overload and transformer load imbalance. In this context, this paper proposes a double-layer master–slave game model of power-water interaction and coordination between distribution network and agricultural irrigation park under photovoltaic (PV) assisted agricultural precision irrigation. The upper layer (electrical distribution network) plays an interactive game with the lower layer (agricultural irrigation parks) by establishing effective time-of-use (TOU) price. On the one hand, the electrical distribution network takes the operation security as the optimization objective, it could optimize line loss by network configuration and guides agricultural irrigation parks to consume electricity orderly by formulating electricity prices. On the other hand, agricultural irrigation parks take satisfaction and cost as the optimization objective after receiving TOU price from upper layer, and regulates the operation time and intensity of irrigation pumps to realize precise irrigation. Finally, an example is given to verify the model on the modified 148-node system. It is determined that the model can effectively support the safe and reliable operation of rural distribution network while realizing the transformation of agricultural irrigation water use from low efficiency to economical and high efficiency, so as to achieve win–win between agricultural irrigation park and distribution network.

Abstract Kagome lattices of various transition metals are versatile platforms for achieving anomalous Hall effects, unconventional charge-density wave orders and quantum spin liquid phenomena due to the strong correlations, spin-orbit coupling and/or magnetic interactions involved in such a lattice. Here, we use laser-based angle-resolved photoemission spectroscopy in combination with density functional theory calculations to investigate the electronic structure of the newly discovered kagome superconductor CsTi3Bi5, which is isostructural to the AV3Sb5 (A = K, Rb or Cs) kagome superconductor family and possesses a two-dimensional kagome network of titanium. We directly observe a striking flat band derived from the local destructive interference of Bloch wave functions within the kagome lattice. In agreement with calculations, we identify type-II and type-III Dirac nodal lines and their momentum distribution in CsTi3Bi5 from the measured electronic structures. In addition, around the Brillouin zone centre, $${{\mathbb{Z}}}_{2}$$ Z 2 nontrivial topological surface states are also observed due to band inversion mediated by strong spin-orbit coupling.

Abstract Background To dynamically monitor the changes of genomic characteristics during lorlatinib treatment and analyze the resistance profile of lorlatinib in ALK‐positive advanced Chinese patients with non‐small cell lung cancer (NSCLC) with first‐ and second‐generation ALK inhibitor resistance. Methods Ten eligible patients who were from a phase 2 study in China and admitted to the Fifth Medical Center of PLA General Hospital were analyzed. Blood samples were collected for next‐generation sequencing (NGS) to characterize genetic variation at baseline, during treatment, and after disease progression. Results Among the 10 patients treated with lorlatinib, objective response rate (ORR) was 50%. The median progression‐free survival (PFS) was 13.3 months, and median overall survival (OS) was 15.6 months. At baseline, the mutation frequency of ALK in circulating tumor DNA (ctDNA) was higher in the group who received two lines of previous anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs), and a similar trend was observed for TP53. After one follow‐up cycle, the decreased variant allele frequency (VAF) had a trend to be predictive for responses. In six patients in which blood samples had been taken after lorlatinib resistance, ALK compound mutations were found in three patients (50%), which were G1202R/L1196M, L1196M/D1203N, and G1202R/F1174C. The DNMT3A N403Tfs*4, ERCC3 E259D, and GNAS p.A436_P459del variants were only detected after progression in two of the other three patients without ALK compound mutations. Conclusions The dynamic changes of genomic characteristics during lorlatinib treatment revealed the mutation landscape of Chinese patients with NSCLC after ALK‐TKI resistance, indicated that the resistance profile of lorlatinib were heterogeneous, which laid the foundation for subsequent treatment to overcome lorlatinib resistance.

Understanding soil phosphorus (P) distribution and its key drivers is fundamental for sustainable P management. In this study, a 21-year fertilization experiment on black soil was carried out, setting up five fertilization treatments: unfertilized control (CK), nitrogen and potassium (NK), nitrogen, P and potassium (NPK), NPK plus straw (NPKS), and NPK plus manure (NPKM). The distribution and effecting factors of P pools within soil aggregates were investigated. Compared to CK, the NK and NPK treatments decreased calcium-associated P concentration in all aggregate fractions. Meanwhile, the NPK treatment significantly increased the organic P extracted from NaOH in unaggregated particles (3, and NaOH increased as aggregate size increased. This was mainly because straw or manure addition promoted soil organic carbon (SOC) storage in aggregates, creating more sorption sites via association with amorphous metallic minerals, and, thus, facilitating P accumulation. In conclusion, decreasing soil pH by chemical fertilizers is an effective strategy for mobilizing soil P, whereas increasing SOC by straw or manure facilitates P accumulation.

With the progress of molecular diagnosis research on non-small cell lung cancer (NSCLC) cells, four identified categories of microRNAs have been found to be related to disease diagnosis, diagnosis of treatment resistance, prediction of prognosis, and drugs for treatment. To date, nine target mRNA/signal pathways have been confirmed for microRNA drug therapy both in vitro and in vivo. When microRNA drugs enter blood vessels, they target the tumor site and play a similar role to that of targeted drugs. However, whether they will produce serious off-target effects remains unknown, and further clinical research is needed. This review provides the first summary of microRNA therapy for NSCLC.

Diabetes mellitus is a chronic metabolic disease, characterized by high blood sugar levels; it affects more than 500 million individuals worldwide. Type 1 diabetes mellitus (T1DM) is results from insufficient insulin secretion by islets; its treatment requires lifelong use of insulin injections, which leads to a large economic burden on patients. Islet transplantation may be a promising effective treatment for T1DM. Clinically, this process currently involves directly infusing islet cells into the hepatic portal vein; however, transplantation at this site often elicits immediate blood-mediated inflammatory and acute immune responses. Subcutaneous islet transplantation is an attractive alternative to islet transplantation because it is simpler, demonstrates lower surgical complication risks, and enables graft monitoring and removal. In this article, we review the current methods of subcutaneous device-free islet transplantation. Recent subcutaneous islet transplantation techniques with high success rate have involved the use of bioengineering technology and biomaterial cotransplantation—including cell and cell growth factor co-transplantation and hydrogel– or simulated extracellular matrix–wrapped subcutaneous co-transplantation. In general, current subcutaneous device-free islet transplantation modalities can simplify the surgical process and improve the posttransplantation graft survival rate, thus aiding effective T1DM management.

With the construction of the power Internet of Things (IoT), communication between smart devices in urban distribution networks has been gradually moving towards high speed, high compatibility, and low latency, which provides reliable support for reconfiguration optimization in urban distribution networks. Thus, this study proposed a deep reinforcement learning based multi-level dynamic reconfiguration method for urban distribution networks in a cloud-edge collaboration architecture to obtain a real-time optimal multi-level dynamic reconfiguration solution. First, the multi-level dynamic reconfiguration method was discussed, which included feeder-, transformer-, and substation-levels. Subsequently, the multi-agent system was combined with the cloud-edge collaboration architecture to build a deep reinforcement learning model for multi-level dynamic reconfiguration in an urban distribution network. The cloud-edge collaboration architecture can effectively support the multi-agent system to conduct “centralized training and decentralized execution” operation modes and improve the learning efficiency of the model. Thereafter, for a multi-agent system, this study adopted a combination of offline and online learning to endow the model with the ability to realize automatic optimization and updation of the strategy. In the offline learning phase, a Q-learning-based multi-agent conservative Q-learning (MACQL) algorithm was proposed to stabilize the learning results and reduce the risk of the next online learning phase. In the online learning phase, a multi- agent deep deterministic policy gradient (MADDPG) algorithm based on policy gradients was proposed to explore the action space and update the experience pool. Finally, the effectiveness of the proposed method was verified through a simulation analysis of a real-world 445-node system.

Objective To genetically analyze the Del sample from a blood donor in Jiangyin and make clear the molecular basis of the serological phenotype. Methods The EDTA anticoagulant blood were collected: buffy coat were used for nucleic acid extract and cDNA analysis; red blood cells for serological test. Tube method and microcolumn gel were used for serological test. Genotyping kit were used for exon analysis. Gene mutation was analyzed using the sequence analyzer. Results Serological analysis demonstrated the sample′s RhD phenotype was Del. The phenotype of RhCE was CCEe. Real-time fluorescence quota PCR result demonstrated the existence of all exones. Weak D15 and RHD*DEL1 [RHD(1227G>A)], which had a high frequency of occurrence in China, were excluded according to real-time fluorescence quota PCR result. Sequence analyzing result verified RHD(28C>T) SNP mutation in cDNA. The genotype of this sample was RHD*01 W. 61[RHD(28C>T)]. Conclusion A weak D61 was found among blood donors in our city, Jiangyin.

Abstract Background Pain is a fearful yet common symptom among lung cancer patients. This multicenter, cross‐sectional study was conducted to examine the current status of pain prevalence and management in lung cancer patients in northern China. Methods A total of 18 hospitals across northern China were selected. Patients with primary lung cancer who visited the outpatient clinic or were admitted in the wards on a preplanned day were invited to complete a questionnaire. Meanwhile, physicians who had experience of treating primary lung cancer patients were also surveyed. Results A total of 533 patients and 197 physicians provided valid responses to the survey, of which 45.4% (242/533) of patients reported pain during the course of disease and 24.2% (129/533) of patients had experienced pain within the past 24 h. The mean average pain intensity by the brief pain inventory was 3.47 ± 1.55. The binary logistic regression analysis showed female gender and stage IV disease were significantly associated with the presence of pain. A total of 74.4% (96/129) of patients reporting pain within 24 h were taking analgesics. The most common reason for patients not using analgesics was that the pain was tolerable (48.2%), while the most common barriers to prescribing opioids as reported by physicians were fear of adverse reactions (43.7%) and fear of addiction (43.1%). Conclusion Despite recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. High‐quality pain education for both patients and physicians is needed in the future.

Abstract Background The efficacy difference between the second‐ and third‐generation of anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs) after crizotinib failure in advanced ALK‐positive non–small cell lung cancer (NSCLC) has not been clarified. This study evaluates the efficacy of different sequential patterns after crizotinib progression. Methods Data of patients who met the study criteria were retrospectively analyzed. The Kaplan–Meier method was used to draw survival curves, log‐rank method was used to compare the differences between groups, and Cox multivariate analysis was used to evaluate the significance of influencing factors. Results A total of 128 patients developed disease progression after crizotinib. The overall survival (OS) of 57 patients in the sequential second‐generation ALK‐TKIs group was significantly longer than that of 65 patients with other systemic treatment (58.5 months vs. 33.0 months, p

Power sharing can improve the benefit of the multimicro grid (MMG) system. However, the information disclosure may appear during the sharing process, which would bring privacy risk to a local microgrid. Actually, the risk and coordination cost are different in different sharing modes. Therefore, this paper develops a decision-making method to decide the most suitable one of three mostly used sharing modes (i.e., cooperative game with complete information, cooperative game with incomplete information, and noncooperative game). Firstly, power sharing paradigms and coordination mechanisms in the three modes are formulated in detail. Particularly, different economic operation models of MMG system are included to analyze the economic benefit from different sharing modes. Based on the different disclosed information, the risk cost is evaluated by using the simplified fuzzy analytic hierarchy process (FAHP). And the coordination cost for different sharing modes is expressed in different functions. In addition, a hierarchical evaluation system including three decision-making factors (e.g., economics, risk, and coordination) is set up. Meanwhile, a combination weighting method (e.g., the simplified FAHP combined with the anti-entropy weight method) is applied to obtain the weight of each factor for comprehensive evaluation. Finally, the optimal sharing solution of MMG system is decided by comparing and analyzing the difference among the three sharing modes. Numerical results validate that the proposed method can provide a reference to deciding a suitable sharing mode.

The increasing integration of photovoltaic generators (PVGs) and the uneven economic development in different regions may cause the unbalanced spatial-temporal distribution of load demands in an urban distribution network (UDN). This may lead to undesired consequences, including PVG curtailment, load shedding, and equipment inefficiency, etc. Global dynamic reconfiguration provides a promising method to solve those challenges. However, the power flow transfer capabilities for different kinds of switches are diverse, and the willingness of distribution system operators (DSOs) to select them is also different. In this paper, we formulate a multi-objective dynamic reconfiguration optimization model suitable for multi-level switching modes to minimize the operation cost, load imbalance, and the PVG curtailment. The multi-level switching includes feeder-level switching, transformer-level switching, and substation-level switching. A novel load balancing index is devised to quantify the global load balancing degree at different levels. Then, a stochastic programming model based on selected scenarios is established to address the uncertainties of PVGs and loads. Afterward, the fuzzy c-means (FCMs) clustering is applied to divide the time periods of reconfiguration. Further-more, the modified binary particle swarm optimization (BPSO) and Cplex solver are combined to solve the proposed mixed-in-teger second-order cone programming (MISOCP) model. Numerical results based on the 148-node and 297-node systems are obtained to validate the effectiveness of the proposed method.

Abstract Background detection of anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements in patients with non‐small‐cell lung cancer (NSCLC) has become a routine pathological diagnosis worldwide. Methods there are three major conventional diagnostic methods for ALK fusions: fluorescent in situ hybridization (FISH); immunohistochemistry (Ventana IHC (D5F3)); and polymerase chain reaction (PCR). Next‐generation sequencing (NGS) technology as is a new tool for ALK status detection with great potential. These four methods are highly consistent in detecting ALK status (coincidence rate >96%). However, discrepancies in ALK status have been found in some patients among these methods, which causes confusion for clinicians. Results and conclusion in this study, we analyzed two patients whose ALK statuses were not consistent using these four methods. We explored the potential reasons for deviation of the test results and found a novel EML4‐ALK break site, which had been not described previously.

Abstract To enable reliable power delivery through transmission tie‐lines, total transfer capability (TTC) must be calculated and regulated to accommodate the transferred amount. However, the traditional optimal power flow (OPF)‐based total transfer capability calculation is computationally expensive for efficient total transfer capability control due to the inclusion of a large set of differential‐algebraic equations (DAEs) to verify transient stability constraints. In order to enable practicable total transfer capability regulation, a novel risk‐aware deep learning‐assisted paradigm is proposed here. First, a deep belief network (DBN) is employed to establish the total transfer capability predictor and surrogate the computation‐intensive differential‐algebraic equations in original optimal power flow formulas, simplifying the high‐dimensional and intractable constraints deep belief networks without loss of nonlinearity. Particularly, in order to be aware of control risk from the predictive error of the deep belief networks, prediction intervals (PIs) are produced improved by using ensemble learning and used to disclose the probability of insufficient actions, further guaranteeing the sufficient and cost‐effective control by compromising the tradeoff between cost and risk. Symbiotic organisms search (SOS) is then applied to solve the proposed risk‐aware deep belief network‐assisted total transfer capability control problem globally. The numerical studies testify that the proposed method enables economical, reliable, and full nonlinearity‐retained dynamic total transfer capability regulation control within a risk‐free surrogate‐assisted and tractable physical model‐driven hybrid framework.

Demand response, the reactive power output of distributed generation (DG), and network reconfiguration have significant impacts on a DG allocation strategy. In this context, a novel real-time price-based demand response formulation is integrated into the allocation model of DG. The tariff is regulated by the difference between the load and active power of renewable energy. Meanwhile, network reconfiguration and the capacity curve describing the active and reactive power limits of DG are included in the optimization model for promoting the allocation of DG. With these measures, the optimal allocation model of DG is established with the goal of maximizing the net annual profit while guaranteeing the efficient utilization of renewable energy. In addition, the uncertainties of renewable energy are considered on the basis of a two-stage robust optimization method. Finally, the entire optimization model is solved by the column and constraint generation algorithm in the IEEE 33-bus distribution system and a practical 99-bus distribution system. Numerical simulations show that the proposed model is effective in terms of improving both the usage of renewable energy and net annual profit.

A field experiment lasting 37 years was conducted to evaluate the applications of different rates of pig manure and mineral fertilisers alone or in combination impacts on total phosphorus (Ptotal) and Olsen phosphorus (POlsen) contents and phosphorus activity coefficient (PAC, percentage of POlsen to Ptotal) within soil water-stable aggregates (WSA) in a Mollisol of Northeast China. The contents of Ptotal and POlsen associated with different size classes of WSA significantly (P < 0.05) increased with an increasing rate of applied P. The application of manure alone or combined with mineral fertilisers significantly increased PAC value associated with different size classes of WSA. There were positive correlations between Ptotal and POlsen contents with soil organic carbon (SOC) content within soil WSA. As SOC content increased 1 g/kg, Ptotal and POlsen contents increased 0.06-0.10 g/kg and 7.69-22.2 mg/kg, respectively, and the increase was larger in smaller size classes of WSA. The results suggested that a high manure rate combined with mineral fertilisers is more beneficial for increasing soil phosphorus content and availability. SOC is a vital factor controlling phosphorus content and availability within soil WSA.

Background This study aimed to investigate the prognostic value of baseline hemoglobin‐to‐red blood cell distribution width ratio (HRR) in patients with small cell lung cancer (SCLC). Methods We retrospectively analyzed the medical records of patients with newly diagnosed SCLC who had received first‐line chemotherapy at the Department of Pulmonary Oncology of the PLA 307 Hospital between January 2008 and October 2018. The optimal cutoff value of the continuous variables was determined using the X‐tile software. Univariate and multivariate analyses were conducted using Cox proportional hazard models. The Kaplan‐Meier method was used for survival analysis, with differences tested using the log‐rank test. Results A total of 146 patients were included. The cutoff value for HRR was determined as 0.985. Statistically significant differences were observed in sex, smoking history, stage, radiotherapy combination, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, hemoglobin, and red blood cell distribution width between the high and low HRR groups. The median overall survival (OS) was nine and 17.5 months in the low and high HRR groups, respectively (P

Background Epidermal growth factor receptor (EGFR) gene mutations predict tumor response to EGFR tyrosine kinase inhibitors (EGFR‐TKIs) in non‐small cell lung cancer (NSCLC). However, even patients with EGFR‐sensitive mutations in NSCLC have limited efficacy with EGFR‐TKI. Studies have shown that long noncoding RNA (lncRNA) is related to diagnosis and prognosis with NSCLC. This study aimed to explore the correlation between lncRNA in NSCLC patients with EGFR mutation status and EGFR‐TKI efficacy. Methods The amplification‐refractory mutation system method was used to test the EGFR mutation status in tumor tissues and pleural effusions of NSCLC patients. Three EGFR‐mutant patients and three EGFR wild‐type patients were selected. Differential lncRNA was performed on the pleural effusions of the two selected groups of patients using Clariom D Human chip technology. Five lncRNAs significantly associated with EGFR mutation status were screened by FC value and GO analysis, and then evaluated by real‐time quantitative polymerase chain reaction in NSCLC patients' pleural effusions. Three were further analyzed in NSCLC patients' plasma. Results There were 61 significant differences in lncRNA between EGFR mutation‐positive and wild‐type patients. Among them, SCARNA7, MALAT1, NONHSAT017369, NONHSAT051892, and FTH1P2 were significantly associated with EGFR mutation status. SCARNA7, MALAT1, and NONHSAT017369 showed consistent results with plasma in pleural effusions compared to EGFR wild‐type, all upregulated in the EGFR mutation group. Conclusion This study shows that lncRNAs can be used not only as potential biomarkers for predicting the mutation status of EGFR and the efficacy of EGFR‐TKI, but also for monitoring the efficacy of EGFR‐TKI.

Background: We compared the efficacy, safety, and immunogenicity of MIL60 with reference bevacizumab as first-line treatment in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in this phase 3, randomized, double-blind study. Methods: Patients with untreated advanced or recurrent NSCLC were randomized (1:1 ratio) to receive either MIL60 or bevacizumab in combination with paclitaxel/carboplatin. Patients with non-progressive disease continued maintenance single-agent MIL60 until disease progression, or intolerable toxicity. The primary endpoint was the 12-week objective response rates (ORR12) by independent review committee (IRC) using RECIST 1.1. Bioequivalence was established if the ORR ratio located between 0.75 and 1/0.75. The trial was registered with clinicaltrials.gov (NCT03196986). Findings: Between Aug 23, 2017, and May 8, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and bevacizumab group (n=260). In the full analysis set (FAS) population including all randomized and evaluable patients who received at least one dose of MIL60 or bevacizumab, the ORR12 in MIL60 group and bevacizumab group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for bevacizumab. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. No patient detected positive for Anti-drug antibody (ADA). Interpretation: The efficacy, safety and immunogenicity of MIL60 were similar with bevacizumab, providing an alternative treatment option for advanced or recurrent non-squamous NSCLC. Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

Olsen phosphorus (Olsen P) is an important indicator of soil labile phosphorus. Determining the effect of fertilization on Olsen P and P fractions (labile phosphorus, medium labile phosphorus and stable phosphorus) can guide the application of phosphate fertilizer. Therefore, it is of great significance to clarify the changes of Olsen P and P fractions and the influencing factors under long-term fertilization. This study investigated changes in Olsen P and P fractions in haplic phaeozems soils (0–20 cm) in two 30-year fertilization sites (Harbin, Gongzhuling) of northern China. Four treatments were examined: treatment with no fertilizer or manure (CK), nitrogen and potassium (NK), nitrogen, phosphorus and potassium (NPK), and manure, nitrogen, phosphorus and potassium (MNPK). The results showed that after NK application, Olsen P decreased by an average of 1.5 mg kg−1 for every 100 kg ha−2 of soil phosphorus lost due to continuous phosphorus uptake by the crop; with NPK, Olsen P increased by an average of 17.6 mg kg−1 for every 100 kg ha−2 of P surplus; with MNPK, the increase curve of Olsen P was similar to an S-curve with periods of rapid growth and periods of equilibrium. In the equilibrium period of Olsen P, the equilibrium values were 52.0 and 156.2 mg kg−1 in Harbin and Gongzhuling. After 20 years of long-term different fertilization, labile P (LP), medium labile P (MLP) and stable P (SP) decreased by 21.1, 16.6 and 15.1 mg kg−1 on average for the treatment without P application (NK), and the percentage decreases were 2.8, 5.7 and 2.1%, respectively. With the treatment of NPK, LP and MLP increased by 25.5 and 79.2 mg kg−1, and the percentage increases were 1.8 and 16.1%. With the treatment of MNPK, the increase in LP and MLP was significantly higher than that with NPK. Soil organic carbon (SOC), total nitrogen (TN) and carbon/nitrogen (C/N) had the greatest effects on Olsen P and P fractions and the total contribution rate was >40%. In summary, fertilization system caused significant changes in Olsen P and P fractions. After about 20 years of long-term combined application of MNPK, the growth of Olsen P can be kept constant. SOC and TN had important effects on Olsen P and P fractions in black soil. Therefore, the application of phosphorus fertilizer should be adjusted according to the type and time of fertilization in black soil in order to avoid waste of phosphorus fertilizer.

In this paper, we consider the n(n≥3)dimensional time-dependent Ginzburg–Landau model for superconductivity. First, we obtain a global existence of very weak solutions. Finally we prove a result of weak-very weak uniqueness.

Introduction: Pembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies. Methods: Patients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel. Dual primary end points were overall survival (OS) and progression-free survival (PFS) (based on the Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review). Results: A total of 125 patients were randomized (pembrolizumab–chemotherapy, n = 65; placebo–chemotherapy, n = 60). As of September 30, 2020, median (range) study follow-up was 28.1 (25.1‒40.9) months. Pembrolizumab–chemotherapy improved OS (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.28–0.70) and PFS (HR = 0.35, 95% CI: 0.24–0.52) versus placebo–chemotherapy. Two-year OS and PFS rates for pembrolizumab–chemotherapy versus placebo–chemotherapy were 56.9% versus 31.7% and 24.2% versus 3.3%, respectively. Treatment-related grade 3 to 5 adverse events occurred in 81.5% and 81.7%, respectively. Relative to baseline, pembrolizumab–chemotherapy improved global health status/quality of life scores at week 18 versus placebo–chemotherapy (difference in least squares means = 7.6, 95% CI: 1.5–13.7) and prolonged time to deterioration in cough, chest pain, or dyspnea (HR = 0.50, 95% CI: 0.28–0.89). Conclusions: Pembrolizumab–chemotherapy prolonged survival versus placebo–chemotherapy with manageable toxicity and preserved or improved health-related quality of life in Chinese patients with metastatic squamous NSCLC. These findings support pembrolizumab–chemotherapy as first-line therapy in this population.

Introduction: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. However, whether patients with EGFR mutations can be treated by osimertinib in combination with conventional therapies, remains unknown.Case presentation: We treated a 67-year-old female diagnosed with non-small-cell lung cancer with an EGFR 21 exon L858R–positive mutation. The patient was treated with 80 mg orally administered osimertinib daily, 830 mg pemetrexed, 120 mg cisplatin, and 500 mg bevacizumab. After two cycles of therapy, the patient’s intrapulmonary lesions shrank from 18 × 24 mm to 16 × 4 mm. Moreover, two cycles of evaluation were PR, and four cycles of confirmation were PR. The patient continued to receive the treatments and tolerated them well.Conclusions: The patient benefited from treatment with osimertinib in combination with chemotherapy and bevacizumab.

The formation of charge density waves is a long-standing open problem, particularly in dimensions higher than one. Various observations in the vanadium antimonides discovered recently further underpin this notion. Here, we study the Kagome metal CsV3Sb5 using polarized inelastic light scattering and density functional theory calculations. We observe a significant gap anisotropy with 2Δmax=kBTCDW ≈ 20, far beyond the prediction of mean-field theory. The analysis of the A1g and E2g phonons, including those emerging below TCDW, indicates strong phonon-phonon coupling, presumably mediated by a strong electron-phonon interaction. Similarly, the asymmetric Fano-type lineshape of the A1g amplitude mode suggests strong electron-phonon coupling below TCDW. The large electronic gap, the enhanced anharmonic phonon-phonon coupling, and the Fano shape of the amplitude mode combined are more supportive of a strong-coupling phonon-driven charge density wave transition than of a Fermi surface instability or an exotic mechanism in CsV3Sb5. [ABSTRACT FROM AUTHOR]

In this article, we define the Hilbert-valued stochastic calculus with respect to G-Brownian motion in G-framework. On that basis, we prove the existence and uniqueness of mild solution for a class of neutral stochastic partial functional integro-differential equations driven by G-Brownian motion with non-Lipschitz coefficients. Our results are established by means of the Picard approximation. Moreover, we establish the stability of mild solution. An example is given to illustrate the theory.

Engagement of programmed death 1 receptor (PD-1) and its ligand PD-L1/2 induces a signal transduction pathway that inhibits the activity of tumor-infiltrating cytotoxic T lymphocytes and promotes tumor growth and metastasis. Antibodies blocking PD-1 or PD-L1 can restore antitumor T cell responses and cause long-term remission in a subset of cancer patients with advanced or refractory tumors. In this study, we asked whether PD-L1 vaccination could confer tumor control in mouse tumor models. To address the central tolerance toward self-molecules, we fused the extracellular domain of PD-L1 (PD-L1E) to the C-terminal of the translocation domain of diphtheria toxin (DTT). DTT is able to elicit CD4+ T cell responses required for inducing robust immune responses against self-molecules. The fusion molecule is called DPDL1E. When formulated with incomplete Freund’s adjuvant (IFA), DPDL1E elicited robust immune responses biased toward the Th1 type and inhibited tumor growth in both preventive and therapeutic mouse tumor models. We further showed that the anti-DPDL1E sera blocked PD-L1 binding to PD-1 in vitro. The DPDL1E vaccination increased the levels of tumor-infiltrating T lymphocytes (TILs) and reduced the levels of myeloid-derived suppressor cells (MDSCs) as well as exhausted LAG3+PD-1+ CD8+ T cells. All of these data suggest that DPDL1E vaccination reverses the suppressive phenotype of the tumor microenvironment and that it is a promising strategy for cancer therapy. Keywords: PD-L1, myeloid-derived suppressor cell, tumor-infiltrating lymphocytes, cancer immunotherapy, tumor microenvironment

Background and objective Current research shows that platelet to lymphocyte ratio (PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer (NSCLC) through meta-analysis. Methods Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet (CNKI), China Biomedical Medicine disc (CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival (OS) and disease-free survival (DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk (HR) and 95% confidence interval (95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018. Results We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.69, 95%CI: 1.45-1.97, P

Objective: To analyze changes in immune functions by detecting lymphocyte subsets in the peripheral blood of residents in the vicinity of radon from hot springs. Methods: Two groups were randomly selected; 61 residents in the vicinity of the hot springs were assigned to the radon group, and 51 residents with a similar lifestyle and habits but no contact with hot springs were assigned to the control group. The percentages of lymphocyte subsets (CD3 + , CD4 + CD8 − , CD4 − CD8 + , CD4 + /CD8 + , and TCR/CD3) in the 2 groups were evaluated on a FACS Aria flow cytometer. The absolute values of lymphocytes (LYMPH#) and percentages of lymphocytes (LYMPH%) were measured by an automatic blood analyzer. Results: In the radon group, the numbers of CD3 + ( Z = −0.140, P > .05) and CD4 + CD8 − ( Z = −0.964, P > .05) T cells were higher, as compared with the controls, but this difference was not significant. In addition, the number of CD4 − CD8 + ( t = −2.141, P < .05) T cells was significantly lower in the radon group. Furthermore, the average ratios of CD4 + /CD8 + ( t = −2.201, P < .05) and TCR/CD3 ( t = 2.047, P < .05) cells were significantly higher in the radon group than in the controls. Compared with the control group, the LYMPH# ( t = −0.485, P > .05) and LYMPH% (Z = −0.835, P > .05) showed no significant change. Conclusion: Radon-rich hot springs could alter the proportions of lymphocyte subsets and possibly affect immunologic functions.

Hepatoid adenocarcinoma of lung (HAL) is a rare and aggressive tumor. The current study reported a new HAL case in the right lower lung with high serum α-fetoprotein (AFP) level in a 71-year-old male patient. After the confirmation of morphology and immunohistochemistry, the patient was diagnosed clinically with HAL and treated with radio-frequency ablation. However, the patient whose disease progressed eventually died 4 months after diagnosis. Whole genome sequencing analysis identified a driver gene mutation in the FAT atypical cadherin 1 gene (FAT1) and the copy number loss. The tumor was microsatellite-stable and tumor mutation burden (TMB) was 1.69 mutations/Mb. PD-L1 expression was negative by IHC. Our finding provide further clues for the molecular basis of HAL and the efficacy of immunotherapy needs to be explored.