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Background The lopinavir/ritonavir (LPV/r) -based second-line antiretroviral therapy (ART) has been used for treating HIV/AIDS patients in China for more than 10 years, but post-therapy immunological non-response (INR) in these patients has been rarely studied. Objective To explore the prevalence and influencing factors of post-therapy INR in HIV/AIDS patients switching from first- to second-line ART. Methods Data (including general information and three-year follow-up information after switching to second-line ART) were collected from the Database of TCM Treatment for AIDS and AIDS Prevention and Control Information System, involving 3 016 HIV/AIDS patients (baseline CD4+ T cell count50 year : OR=1.81, 95%CI (1.36, 2.42) 〕, route of infection〔blood: OR=1.40, 95%CI (1.06, 1.85) 〕, duration of HIV positive〔3-6 years: OR=1.48, 95%CI (1.02, 2.13) 〕, duration of HAART therapy before switch to second-line ART〔3-5 year: OR=0.66, 95%CI (0.48, 0.90) ; >5 year: OR=0.71, 95%CI (0.53, 0.95) 〕and baseline CD4+ T cells count〔50 year: OR=1.8, 95%CI (1.31, 2.49) 〕, route of infection〔blood: OR=1.45, 95%CI (1.07, 2.00) 〕, baseline CD4+ T cell count〔

Abstract Background Process and function that underlie the assembly of a rhizosphere microbial community may be strongly linked to the maintenance of plant health. However, their assembly processes and functional changes in the deterioration of soilborne disease remain unclear. Here, we investigated features of rhizosphere microbiomes related to Fusarium wilt disease and assessed their assembly by comparison pair of diseased/healthy sequencing data. The untargeted metabolomics was employed to explore potential community assembly drivers, and shotgun metagenome sequencing was used to reveal the mechanisms of metabolite-mediated process after soil conditioning. Results Results showed the deterministic assembly process associated with diseased rhizosphere microbiomes, and this process was significantly correlated to five metabolites (tocopherol acetate, citrulline, galactitol, octadecylglycerol, and behenic acid). Application of the metabolites resulted in a deterministic assembly of microbiome with the high morbidity of watermelon. Furthermore, metabolite conditioning was found to weaken the function of autotoxin degradation undertaken by specific bacterial group (Bradyrhizobium, Streptomyces, Variovorax, Pseudomonas, and Sphingomonas) while promoting the metabolism of small-molecule sugars and acids initiated from another bacterial group (Anaeromyxobacter, Bdellovibrio, Conexibacter, Flavobacterium, and Gemmatimonas). Video Abstract Conclusion These findings strongly suggest that shifts in a metabolite-mediated microbial community assembly process underpin the deterministic establishment of soilborne Fusarium wilt disease and reveal avenues for future research focusing on ameliorating crop loss due to this pathogen.

Background: Several studies have highlighted the incidence of Clostridioides difficile infections (CDIs) in Taiwan and certain ribotypes have been related to severe clinical diseases. A study was conducted to investigate the polymerase chain reaction (PCR) ribotypes and genetic relatedness of clinical C. difficile strains collected from January 2009 to December 2015 at a hospital in northeastern Taiwan. Material and methods: A modified two-step typing algorithm for C. difficile was used by combining a modified 8-plex and 3′-truncated tcdA screening PCR. In addition, MLVA typing was adopted for investigation of bacterial clonality and transmission. Results: Among a total of 86 strains, 24 (28%) were nontoxigenic and 62 (72%) had both tcdA and tcdB (A + B+). No tcdA-negative and tcdB-positive (A−B+) strains were identified. Binary toxin (CDT)-producing (cdtA+/cdtB+) strains were started to be identified in 2013. The 21 (34%) A+B+ clinical strains with binary toxin and tcdC deletion were identified as RT127 strains, which contained both RT078-lineage markers and fluoroquinolone (FQ)-resistant mutations (Thr82Ile in gyrA). Multiple loci variable-number tandem repeat analysis (MLVA) for phylogenetic relatedness of RT127 strains indicated that 20 of 21 strains belonged to a clonal complex that was identical to a clinical strain collected from southern Taiwan in 2011, suggestive of a clonal expansion in Taiwan. Conclusion: A two-step typing method could rapidly confirm species identification and define the toxin gene profile of C. difficile isolates. The clonal expansion of RT127 strains in Taiwan indicates monitoring and surveillance of toxigenic C. difficile isolates from human, animal, and environment are critical to develop One Health prevention strategies.

Plant roots are one of the major mediators that allocate carbon captured from the atmosphere to soils as rhizodeposits, including root exudates. Although rhizodeposition regulates both microbial activity and the biogeochemical cycling of nutrients, the effects of particular exudate species on soil carbon fluxes and key rhizosphere microorganisms remain unclear. By combining high-throughput sequencing, q-PCR, and NanoSIMS analyses, we characterized the bacterial community structure, quantified total bacteria depending on root exudate chemistry, and analyzed the consequences on the mobility of mineral-protected carbon. Using well-controlled incubation experiments, we showed that the three most abundant groups of root exudates (amino acids, carboxylic acids, and sugars) have contrasting effects on the release of dissolved organic carbon (DOC) and bioavailable Fe in an Ultisol through the disruption of organo-mineral associations and the alteration of bacterial communities, thus priming organic matter decomposition in the rhizosphere. High resolution (down to 50 nm) NanoSIMS images of mineral particles indicated that iron and silicon co-localized significantly more organic carbon following amino acid inputs than treatments without exudates or with carboxylic acids. The application of sugar strongly reduced microbial diversity without impacting soil carbon mobilization. Carboxylic acids increased the prevalence of Actinobacteria and facilitated carbon mobilization, whereas amino acid addition increased the abundances of Proteobacteria that prevented DOC release. In summary, root exudate functions are defined by their chemical composition that regulates bacterial community composition and, consequently, the biogeochemical cycling of carbon in the rhizosphere.

Objectives: Interferon-γ release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the COVID-19 pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. Methods: We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. Results: A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analyzed. Among the baseline IGRA-negative cases, there were decreased interferon-γ concentrations over the Nil (P = 0.005) and increased Mitogen-Nil (P < 0.001) values after vaccination. For TB2-Nil value, a similar trend (P = 0.057) of increase was observed. Compared with the 0.35 IU/ml threshold, the baseline and follow-up readout differences were less than |± 0.10| IU/ml over the TB1-Nil and TB2-Nil values in >90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRA-positive cases. Conclusion: COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration.

The combination of high pressure and severe plastic deformation in the process of high-pressure torsion in a rotational diamond anvil cell (RDAC) produces a variety of important mechanical and chemical effects. In this Review, mechanochemical phenomena that appeared with compression and plastic shear of samples in RDAC have been systematized, which are associated with strain-induced structural changes (SCs) under high pressure and shear, containing phase transitions (PTs) and chemical reactions (CRs). This Review aims to summarize the current phenomena based on the results of multiscale atomic and continuum theory and macroscale modeling. By analyzing and using the advanced phase field theory and simulation, the nano-scale mechanism of phase nucleation induced by plastic strain was studied. The results show that the concentration of the stress tensor near the edge dislocation stacking tip may reduce the nucleation pressure by ten times or more. These results promote the development of a microscopic analysis dynamic equation of strain-induced PTs. On the micro-scale, a simple strain control dynamic kinetics of strain-induced SCs is derived by thermodynamics. On the macro-scale, a macro-model of pressure and strain-induced PTs in RDAC is established based on the finite element method, and it could be used to explain various experimental phenomena. The application of RDAC provides important insights for the coupling of PT and material plastic flow, which is of great significance for optimizing the experimental design and extracting PT parameters of materials, as well as optimizing and controlling PT.

Objectives Personal health literacy is the degree to which individuals have the ability to find, understand and use information and services to inform health-related decisions and actions for themselves and others. Health literacy levels remain low, despite the many measures that have been taken to improve it. In addition, the number of patients with chronic diseases is increasing. Our study aimed to explore the different aspects and factors influencing health literacy among patients with chronic diseases in Chongqing, China.Design Cross-sectional study.Setting and patients This study was conducted in Chongqing using the 2018 National Questionnaire on Health Literacy of Residents administered to 27 336 patients with chronic diseases.Outcome measures The prevalence and factors of health literacy in patients with chronic diseases.Results Among the patients who participated in the study (n=27 336), 51.3% were males. Only 21.6% of the patients with chronic diseases had adequate health literacy (questionnaire score was equal to or exceeded 80% of the total questionnaire score). Patients with chronic diseases aged 25–34 years (OR=1.18, 95% CI 1.02 to 1.36) and 35–44 years (OR=1.18, 95 % CI 1.03 to 1.35) had higher health literacy than patients aged 65–69 years. Patients from rural areas had higher health literacy levels than those from urban areas (OR=0.92, 95% CI 0.86 to 1.00). Furthermore, married patients had lower health literacy than unmarried patients (OR=0.88, 95% CI 0.80 to 0.97). Patients who were illiterate or slightly literate (OR=0.10, 95% CI 0.08 to 0.12) had lower health literacy than patients who were in junior college or had a bachelor’s degree or above. In addition, non-farmers had higher health literacy levels than farmers (OR=1.18, 95% CI 1.08 to 1.28). In terms of inadequate health literacy, patients who self-rated themselves as healthy had higher health literacy than those who self-rated as unhealthy (OR=1.80, 95% CI 1.33 to 2.43).Conclusions The health literacy of patients with chronic conditions remains at a low level and varies significantly with their demographic and social characteristics. These findings indicate that targeted interventions may be useful to improve health literacy in patients with chronic conditions in China.

ABSTRACT Seed-associated microbiomes can impact the later colonization of a plant rhizosphere microbiome. However, there remains little insight into the underlying mechanisms concerning how alterations in the composition of the seed microbiome may intervene in the assembly of a rhizosphere microbiome. In this study, the fungus Trichoderma guizhouense NJAU4742 was introduced to both maize and watermelon seed microbiomes by seed coating. Application was found to significantly promote seed germination and improve plant growth and rhizosphere soil quality. The activities of acid phosphatase, cellulase, peroxidase, sucrase, and α-glucosidase increased significantly in two crops. The introduction of Trichoderma guizhouense NJAU4742 also led to a decrease in the occurrence of disease. Coating with T. guizhouense NJAU4742 did not alter the alpha diversities of the bacterial and fungal communities but formed a key network module that contained both Trichoderma and Mortierella. This key network module comprised of these potentially beneficial microorganisms was positively linked with the belowground biomass and activities of rhizosphere soil enzymes but negatively correlated with disease incidence. Overall, this study provides insights into plant growth promotion and plant health maintenance via seed coating in order to influence the rhizosphere microbiome. IMPORTANCE Seed-associated microbiomes can impact the rhizosphere microbiome assembly and function display. However, there remains little insight into the underlying mechanisms concerning how alterations in the composition of the seed microbiome with the beneficial microbes may intervene in the assembly of a rhizosphere microbiome. Here, we introduced T. guizhouense NJAU4742 to the seed microbiome by seed coating. This introduction led to a decrease in the occurrence of disease and an increase in plant growth; furthermore, it formed a key network module that contained both Trichoderma and Mortierella. Our study provides insights into plant growth promotion and plant health maintenance via seed coating in order to influence the rhizosphere microbiome.

ObjectiveTo observe the effect of beinaglutide combined with metformin versus metformin alone on weight loss and metabolic profiles in obese patients with polycystic ovary syndrome(PCOS).MethodsA total of 64 overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomly assigned to metformin(MET) 850 mg twice a day(BID) or combined MET 850 mg BID with beinaglutide (COMB) starting at 0.1mg three times a day(TID)and increasing to 0.2mg TID two weeks later. The main endpoints were changes in anthropometric measurements of obesity. Glucose and lipid metabolic, gonadal profiles, and antral follicle count changes as secondary outcomes were also observed.Results60(93.75%) patients completed the study. In terms of lowering weight, body mass index (BMI),waist circumference(WC) and waist to height ratio(WHtR), COMB treatment outperformed MET monotherapy. Subjects in the COMB arm lost weight 4.54±3.16kg compared with a 2.47±3.59kg loss in the MET arm. In the COMB group, BMI,WC and WHtR were reduced significantly compared with that in the MET group, respectively. COMB therapy is also more favorable in the reduction of fasting insulin(FINS), total testosterone(TT), and homeostasis model assessment–insulin resistance(HOMA-IR) when compared to MET therapy. Antral follicle count and ovarian volume were non-significantly changed in both groups.The most frequent side effects in both groups were mild and moderate digestive symptoms. Itching and induration at the injection site were reported with COMB treatment.ConclusionShort-term combined treatment with beinaglutide and metformin appears superior to metformin monotherapy in lowering body weight, BMI, WC,WHtR and improving insulin sensitivity and androgen excess in women with PCOS and obesity, with tolerable adverse events.Clinical trial registrationhttps://www.chictr.org.cn/listbycreater.aspx, identifier ChiCTR2000033741.

Tetrodotoxin (TTX) could result in serious diseases due to its extremely high neurotoxicity. Thus, it is of great importance to measure TTX for food safety. In this study, an anti-TTX monoclonal antibody with good specificity and high affinity was used to develop the immunochromatographic test strips (ICTS). Gold nanoflower (AuNF) with multiple branches and latex microsphere (LM) with large particle size as signal reporters were employed for improving the sensitivity of test strips. Both AuNF and LM probes are stable, and the developed ICTS were specific to TTX, demonstrating no cross-reactivity with other marine toxins. The linear range of AuNF- and LM-based strips for TTX was 9.49–330.98 ng/mL and 5.40–443.19 ng/mL, respectively. The limit of detection (LOD) of AuNF- and LM-based strips was determined to be 9.49 ng/mL and 5.40 ng/mL, respectively. In summary, the developed ICTS based on AuNF and LM signal probes displayed enhancement of sensitivity and provided rapid and specific detection of TTX.

Obesity is a complex metabolic disease, with cognitive impairment being an essential complication. Gut microbiota differs markedly between individuals with and without obesity. The microbial–gut–brain axis is an important pathway through which metabolic factors, such as obesity, affect the brain. Probiotics have been shown to alleviate symptoms associated with obesity and neurobehavioral disorders. In this review, we evaluated previously published studies on the effectiveness of probiotic interventions in reducing cognitive impairment, depression, and anxiety associated with obesity or a high-fat diet. Most of the probiotics studied have beneficial health effects on obesity-induced cognitive impairment and anxiety. They positively affect immune regulation, the hypothalamic–pituitary–adrenal axis, hippocampal function, intestinal mucosa protection, and glucolipid metabolism regulation. Probiotics can influence changes in the composition of the gut microbiota and the ratio between various flora. However, probiotics should be used with caution, particularly in healthy individuals. Future research should further explore the mechanisms underlying the gut–brain axis, obesity, and cognitive function while overcoming the significant variation in study design and high risk of bias in the current evidence.

Oil tea (Camellia oleifera Abel.), an important edible oil tree found in the acidic soil of south China, is tolerant to aluminum (Al); however, the mechanism via which it detoxifies Al remains unclear. The present study investigated the accumulation and distribution of Al and the changes in antioxidant components in C. oleifera leaves at different stages of growth. The analysis revealed that the content of Al in young, mature, and old leaves was 1.53, 7.49, and 12.04 g kg−1, respectively. In the leaves, Al was mainly accumulated in the cell wall, which accounted for 66.03%, 79.94%, and 86.51% of the total Al accumulation in young, mature, and old leaves, respectively. In the leaf cell wall, the Al content in hemicellulose increased from 54.22% to 81.72% with leaf age. The proportion of Al in the upper epidermis, lower epidermis, palisade, and spongy parenchyma cell walls increased with leaf age. The activity of antioxidant enzymes increased and showed a synergistic effect on Al stress with leaf age. The peroxidase activity was the highest in mature leaves, 2.3 times that in young leaves. Meanwhile, catalase and superoxide dismutase activities and total phenol content were the highest in young leaves. Correlation analysis showed that antioxidant system composed of catalase, superoxide dismutase and total phenol (CAT, SOD, and TP) was negatively correlated with the Al content in C. oleifera leaves. The malondialdehyde (MDA) content was positively correlated with Al content in C. oleifera leaves, indicating that the MDA in the leaves helped resist Al stress in C. oleifera. Thus, our findings suggest that the increase in antioxidant properties and modification of the cell wall contributed to Al detoxification in the Al hyperaccumulator C. oleifera.

As a filamentous pathogenic fungus with high-yield of aflatoxin B1, Aspergillus flavus is commonly found in various agricultural products. It is crucial to develop effective strategies aimed at the prevention of the contamination of A. flavus and aflatoxin. Hexokinase AfHxk1 is a critical enzyme in fungal glucose metabolism. However, the role of AfHxk1 in A. flavus development, aflatoxin biosynthesis, and virulence has not yet been explored. In this study, afHxk1 gene deletion mutant (ΔafHxk1), complementary strain (Com-afHxk1), and the domain deletion strains (afHxk1ΔD1 and afHxk1ΔD2) were constructed by homologous recombination. Phenotype study and RT-qPCR revealed that AfHxk1 upregulates mycelium growth and spore and sclerotia formation, but downregulates AFB1 biosynthesis through related classical signaling pathways. Invading models and environmental stress analysis revealed that through involvement in carbon source utilization, conidia germination, and the sensitivity response of A. flavus to a series of environmental stresses, AfHxk1 deeply participates in the regulation of pathogenicity of A. flavus to crop kernels and Galleria mellonella larvae. The construction of domain deletion strains, afHxk1ΔD1 and afHxk1ΔD2, further revealed that AfHxk1 regulates the morphogenesis, mycotoxin biosynthesis, and the fungal pathogenicity mainly through its domain, Hexokinase_2. The results of this study revealed the biological role of AfHxk1 in Aspergillus spp., and might provide a novel potential target for the early control of the contamination of A. flavus.

C6H9N3O3, monoclinic, P21/n (no. 14), a = 9.5584(4) Å, b = 6.7828(3) Å, c = 12.8337(6) Å, β = 103.8810(10)∘, V = 807.74(6) Å3, Z = 4, Rgt(F) = 0.0455, wRref(F2) = 0.1166, T = 170.0 K.

C5H7N3O3, monoclinic, P21/n (no. 14), a = 8.7821(7) Å, b = 7.1320(5) Å, c = 11.6293(10) Å, β = 104.718(3)∘ $104.718{(3)}^{\circ }$ , V = 704.49(10) Å3, Z = 4, Rgt ${R}_{gt}$ (F) = 0.0468, wRref $w{R}_{ref}$ (F 2) = 0.1125, T = 170.0 K.

Nucleic acids from bacteria or viruses induce potent immune responses in infected cells1-4. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses5,6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor7,8. It catalyses the synthesis of cyclic GMP-AMP (cGAMP)9-12, which stimulates the induction of type I interferons through the STING-TBK1-IRF-3 signalling axis13-15. STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the TBK1 kinase8,16. The IRF-3 transcription factor is then recruited to the signalling complex and activated by TBK18,17-20. Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of type I interferons21. However, the precise mechanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain unclear. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for induction of IFNβ after cGAMP stimulation. Moreover, we show that full-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the activation of STING-mediated signalling. These findings provide a structural basis for the development of STING agonists and antagonists for the treatment of cancer and autoimmune disorders.

This article describes the construction of optical solitons and single traveling wave solutions of Biswas-Arshed equation with the beta time derivative. By using the polynomial complete discriminant system method, a series of traveling wave solutions are constructed, including the rational function solutions, Jacobian elliptic function solutions, hyperbolic function solutions, trigonometric function solutions and inverse trigonometric function solutions. The conclusions of this paper comprise some new and different solutions that cannot be found in existing literature. Using the mathematic software Maple, the 3D and 2D graphs of the obtained traveling wave solutions were also developed. It is worth noting that these traveling wave solutions may motivate us to explore new phenomena which may be appear in optical fiber propagation theory.

As a typical active noise control algorithm, Filtered-x Least Mean Square (FxLMS) is widely used in the field of audio denoising. In this study, an audio denoising coprocessor based on Retrenched Injunction System Computer-V (RISC-V), a custom instruction set extension was designed and a software and hardware co-design was adopted; based on the traditional pure hardware implementation, the accelerator optimization design was carried out, and the accelerator was connected to the RISC-V core in the form of coprocessor. Meanwhile, the corresponding custom instructions were designed, the compiling environment was established, and the library function of coprocessor acceleration instructions was established by embedded inline assembly. Finally, the active noise control (ANC) system was built and tested based on Hbird E203-Core, and the test data were collected through an audio analyzer. The results showed that the audio denoising algorithm can be realized by combining a heterogeneous System on Chip (SoC) with a hardware accelerator, and the denoising effect was approximately 8 dB. The number of instructions consumed by testing custom instructions for specific operations was reduced by approximately 60%, and the operation acceleration effect was significant.

The present study sought to explore the deformation and fracture behavior of Quenching and Partitioning (Q&P) steel at five different strain rates (10−4 s−1, 1 s−1, 10 s−1, 100 s−1 and 1400 s−1). Tensile tests were carried out on Q&P steel at different strain rates, and the deformation and fracture behaviors were explored through digital image correlation (DIC) and scanning electron microscope (SEM). The results indicated that the strength and plasticity of Q&P steel had significant strain rate sensitivity. The yield strength and ultimate strength increases continuously, whereas the elongation first decreased and then increased with increase in strain rate. The dimples gradually became smaller and flatter with increase in strain rate. The dislocation density increased when strain rate was above 100 s−1, indicating that resistance to dislocation slip increases and the slip distance becomes shorter at high strain rates, which inhibits generation of large deformation. The local plastic strain at the fracture significantly decreased from 0.7 to 0.3, resulting in partial brittle fracture characteristics in fracture morphology. These findings provide a basis for further elucidating the deformability and fracture behavior of Q&P steel at different strain rates.

ObjectivesSingle-isocentre volumetric-modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance for patients with multiple liver metastases (MLM). However, the potential increase in dose spillage to normal liver tissue using a single-isocentre technique has not yet been studied. We comprehensively evaluated the quality of single- and multi-isocentre VMAT-SBRT for MLM and propose a RapidPlan-based automatic planning (AP) approach for MLM SBRT.MethodsA total of 30 patients with MLM (two or three lesions) were selected for this retrospective study. We manually replanned all patients treated with MLM SBRT by using the single-isocentre (MUS) and multi-isocentre (MUM) techniques. Then, we randomly selected 20 MUS and MUM plans for training to generate the single-isocentre RapidPlan model (RPS) and the multi-isocentre RapidPlan model (RPM). Finally, we used data from the remaining 10 patients to validate RPS and RPM.ResultsCompared with MUS, MUM reduced the mean dose delivered to the right kidney by 0.3 Gy. The mean liver dose (MLD) was 2.3 Gy higher for MUS compared with MUM. However, the monitor units, delivery time, and V20Gy of normal liver (liver-gross tumour volume) for MUM were significantly higher than for MUS. Based on validation, RPS and RPM slightly improved the MLD, V20Gy, normal tissue complications, and dose sparing to the right and left kidneys and spinal cord compared with manual plans (MUS vs RPS and MUM vs RPM), but RPS and RPM significantly increased monitor units and delivery time.ConclusionsThe single-isocentre VMAT-SBRT approach could be used for MLM to reduce treatment time and patient comfort at the cost of a small increase in the MLD. Compared with the manual plans, RapidPlan-based plans, especially RPS, have slightly improved quality.

Non-small cell lung cancer (NSCLC) is a prominent etiology of cancer-related mortality. The heterogeneous nature of this disease impedes its accurate diagnosis and efficacious treatment. Consequently, constant advancements in research are imperative in order to comprehend its intricate nature. In addition to currently available therapies, the utilization of nanotechnology presents an opportunity to enhance the clinical outcomes of NSCLC patients. Notably, the burgeoning knowledge of the interaction between the immune system and cancer itself paves the way for developing novel, emerging immunotherapies for treating NSCLC in the early stages of the disease. It is believed that with the novel engineering avenues of nanomedicine, there is a possibility to overcome the inherent limitations derived from conventional and emerging treatments, such as off-site drug cytotoxicity, drug resistance, and administration methods. Combining nanotechnology with the convergence points of current therapies could open up new avenues for meeting the unmet needs of NSCLC treatment.

We show how reinforcement learning can be used in conjunction with quantile regression to develop a hedging strategy for a trader responsible for derivatives that arrive stochastically and depend on a single underlying asset. We assume that the trader makes the portfolio delta-neutral at the end of each day by taking a position in the underlying asset. We focus on how trades in options can be used to manage gamma and vega. The option trades are subject to transaction costs. We consider three different objective functions. We reach conclusions on how the optimal hedging strategy depends on the trader's objective function, the level of transaction costs, and the maturity of the options used for hedging. We also investigate the robustness of the hedging strategy to the process assumed for the underlying asset.

ObjectiveTo understand the varieties, evaluation, treatment, and prognosis of severe neurological diseases using the third NCU survey in China.DesignA cross-sectional questionnaire study. The study was completed in three main steps: filling in the questionnaire, sorting out the survey data, and analyzing the survey data.ResultsOf 206 NCUs, 165 (80%) provided relatively complete information. It was estimated that 96,201 patients with severe neurological diseases were diagnosed and treated throughout the year, with an average fatality rate of 4.1%. The most prevalent severe neurological disease was cerebrovascular disease (55.2%). The most prevalent comorbidity was hypertension (56.7%). The most prevalent complication was hypoproteinemia (24.2%). The most common nosocomial infection was hospital-acquired pneumonia (10.6%). The GCS, APACHE II, EEG, and TCD were the most commonly used (62.4–95.2%). The implementation rate of the five nursing evaluation techniques reached 55.8–90.9%. Routinely raising the head of the bed by 30°, endotracheal intubation and central venous catheterization were the mostprevalent treatment strategies (97.6, 94.5, and 90.3%, respectively). Traditional tracheotomy, invasive mechanical ventilation and nasogastric tube feeding (75.8, 95.8, and 95.8%, respectively) were more common than percutaneous tracheotomy, non-invasive mechanical ventilation and nasogastric tube insertion (57.6, 57.6, and 66.7%, respectively). Body surface hypothermia brain protection technology was more commonly used than intravascular hypothermia technology (67.3 > 6.1%). The rates of minimally invasive hematoma removal and ventricular puncture were only 40.0 and 45.5%, respectively.ConclusionIn addition to traditional recognized basic life assessment and support technology, it is necessary to the use of promote specialized technology for neurological diseases, according to the characteristics of critical neurological diseases.

Objectives: An outbreak of the SARS-CoV-2 Delta variant occurred in Guangzhou in 2021. This study aimed to identify the transmission dynamics and epidemiological characteristics of the Delta variant outbreak to formulate an effective prevention strategy. Methods: A total of 13102 close contacts and 69 index cases were collected. The incubation period, serial interval, and time interval from the exposure of close contacts to the symptom onset of cases were estimated. Transmission risks based on the exposure time and various characteristics were also assessed. Results: The mean time from exposure to symptom onset among non-household presymptomatic transmission was 3.83 ± 2.29 days, the incubation period was 5 days, and the serial interval was 3 days. The secondary attack rate was high within 4 days before onset and 4–10 days after symptom onset. Compared with other contact types, household contact had a higher transmission risk. The transmission risk increased with the number and frequency of contact with index cases. Cycle threshold (Ct) values were associated with lower transmission risk (adjusted odds ratio [OR] 0.93 [95% CI 0.88–0.99] for ORF 1ab gene; adjusted OR 0.91 [95% CI 0.86–0.97] for N gene). Conclusion: The contact tracing period may need to be extended to 4 days before symptom onset. The low Ct value of index cases, the high number and frequency of contact with index cases, and household contacts were associated with a higher transmission risk of SARS-CoV-2 Delta.