Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery.

Microneedle (MN)-assisted drug delivery technology has gained increasing attention over the past two decades. Its advantages of self-management and being minimally invasive could allow this technology to be an alternative to hypodermic needles. MNs can penetrate the stratum corneum and deliver active ingredients to the body through the dermal tissue in a controlled and sustained release. Long-acting polymeric MNs can reduce administration frequency to improve patient compliance and therapeutic outcomes, especially in the management of chronic diseases. In addition, long-acting MNs could avoid gastrointestinal reactions and reduce side effects, which has potential value for clinical application. In this paper, advances in design strategies and applications of long-acting polymeric MNs are reviewed. We also discuss the challenges in scale manufacture and regulations of polymeric MN systems. These two aspects will accelerate the effective clinical translation of MN products.

Efficacy and Safety of Nimotuzumab in Combination with Radiotherapy or Chemoradiotherapy for Local Advanced Head and Neck Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: The present meta-analysis aimed to evaluate the efficacy and safety of adding nimotuzumab to radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: Prospective randomized controlled studies at EMBASE, PubMed, and the Cochrane Library from January 1, 2010, to October 1, 2022, were searched. Data on the overall survival (OS), progress-free survival (PFS), disease-free survival (DFS), complete response rate (CRR), objective response rate (ORR), and all grade adverse events were collected from the enrolled publications. OS was the primary measurement indicator. Pooled analysis was performed with relative risks (RRs), hazard risks (HRs), and their corresponding 95% confidence intervals (CIs) in the software Stata SE 16.0. RESULTS: Six randomized controlled studies were included in the analysis of the overall pooled effect. As compared to the control group, the nimotuzumab intervention group exhibited improved OS by 21% (pooled HR=0.79,95% CI: 0.64-0.98, P=0.028), along with PFS up to 31% (HR=0.69, 95% CI: 0.55-0.86, P=0.001) and DFS up to 29% (HR=0.71, 95% CI: 0.56-0.91, P=0.006), increased CRR as 50% (RR=1.50, 95%CI:1.09-2.04; P=0.012), and ORR as 35% (RR=1.35, 95%- CI:1.04-1.73; P=0.022). Regarding safety, nimotuzumab in combination with RT or CRT did not increase the incidence of all grade adverse events (pooled-RD=-1.27, 95%CI:-2.78-0.23, P=0.099). CONCLUSION: The present meta-analysis has demonstrated that nimotuzumab, in combination with RT or CRT, could provide survival benefits and increase response rates. Its safety profile has been found to be controllable.

Mitigating salinity stress through interactions between microalgae and different forms (free-living & alginate gel-encapsulated) of bacteria isolated from estuarine environments.

Salinity stress in estuarine environments poses a significant challenge for microalgal survival and proliferation. The interaction between microalgae and bacteria shows promise in alleviating the detrimental impacts of salinity stress on microalgae. Our study investigates this interaction by co-cultivating Chlorella sorokiniana, a freshwater microalga, with a marine growth-promoting bacterium Pseudomonas gessardii, both of which were isolated from estuary. In this study, bacteria were encapsulated using sodium alginate microspheres to establish an isolated co-culture system, preventing direct exposure between microalgae and bacteria. We evaluated microalgal responses to different salinities (5 PSU, 15 PSU) and interaction modes (free-living, gel-encapsulated), focusing on growth, photosynthesis, cellular metabolism, and extracellular polymeric substances (EPS) properties. High salinity inhibited microalgal proliferation, while gel-fixed interaction boosted Chlorella growth rate by 50.7 %. Both attached and free-living bacteria restored Chlorella's NPQ to normal levels under salt stress. Microalgae in the free-living interaction group exhibited a significantly lower respiratory rate compared to the pure algae group (-17.2 %). Increased salinity led to enhanced EPS polysaccharide secretion by microalgae, particularly in interaction groups (19.7 %). Both salt stress and interaction increased the proportion of aromatic proteins in microalgae's EPS, enhancing its stability by modulating EPS glycosidic bond C-O-C and protein vibrations. This alteration caused microalgal cells to aggregate, free-living bacteria co-culture group, and fixed co-culture group increasing by 427.5 %, 567.1 %, and 704.1 %, respectively. In gel-fixed bacteria groups, reduced neutral lipids don't accumulate starch instead, carbon redirects to cellular growth, aiding salt stress mitigation. These synergistic activities between salinity and bacterial interactions are vital in mitigating salinity stress, improving the resilience and growth of microalgae in saline conditions. Our research sheds light on the mechanisms of microalgal-bacterial interactions in coping with salt stress, offering insights into the response of estuarine microorganisms to global environmental changes and their ecological stability.

Assembly dynamics of eukaryotic plankton and bacterioplankton in the Yangtze River estuary: A hybrid community perspective.

Estuaries, acting as transitional habitats receiving species introductions from both freshwater and marine sources, undergo significant impacts from global climate changes. Planktonic microorganisms contribute significantly to estuarine biodiversity and ecological stability. These microorganisms primarily fall into three groups: eukaryotic plankton, particle-associated bacteria, and free-living bacteria. Understanding the structural characteristics and interactions within these subcommunities is crucial for comprehending estuarine dynamics. We collected samples from three distinct locations (< 0.1 PSU, 6.6 PSU, and 19 PSU) within the Yangtze River estuary. Samples underwent analysis for physicochemical indicators, while microbial communities were subjected to 16S/18S rRNA amplicon sequencing. Additionally, simulated mixing experiments were conducted using samples of varying salinities. Estuary samples, combined with simulated experiments, were employed to collectively examine the structural characteristics and assembly processes of estuarine microbes. Our research highlights the considerable impact of phylogenetic classification on prokaryotic behavior in these communities. We observed a transition in assembly processes from primarily stochastic for particle-associated bacteria to a predominant influence of homogeneous selection as salinity increased. Particle-associated bacterial communities exhibited a greater influence of stochastic processes compared to free-living bacteria, showcasing higher stability in diversity. The variations in composition and structure of estuarine microbial subcommunities were influenced by diverse environmental factors. Particle-associated bacteria displayed elevated network characterization values and established closer interactions with eukaryotic plankton. Structural equation modeling (SEM) analysis revealed that free-living bacteria displayed a heightened sensitivity to environmental factors and exerted a more significant influence on assembly processes and network characteristics. Simulated mixing in these environments resulted in the loss of species with similar microbial taxonomic relationships. The functioning of bacterioplankton is influenced by salinity and the processes governing their assembly, particularly in relation to different living states. These findings significantly contribute to our understanding of the intricate interplay between prokaryotic and eukaryotic plankton microorganisms in highly dynamic environments, laying a robust foundation for further exploration into the ecological mechanisms governing microbial dynamics in estuaries.

Massive extrapancreatic solid pseudopapillary neoplasm misdiagnosed as hepatic tumor: a case report and literature review.

Background: Solid pseudopapillary neoplasms (SPNs) of the pancreas are uncommon, low-malignancy neoplasms. Moreover, the occurrence of extrapancreatic SPNs is rarely encountered. Case summary: A 45-year-old female presented with a right upper abdominal mass and abdominal pain for 3 and 1 months as chief complaints, respectively. Initially, the patient was misdiagnosed with hepatocellular carcinoma based on her symptoms and results of physical and imaging examinations. Following multidisciplinary discussion and ruling out surgical contraindications, a decision was taken to proceed with surgical intervention. Interestingly, the tumor was found to originate from the retroperitoneum and had invaded the right half of the liver and the right wall of the inferior vena cava. The operation was uneventful, and the pathological findings confirmed the tumor as an extrapancreatic SPN. The patient remained asymptomatic after 15 months of follow-up. Conclusion: Surgical treatment remains the preferred option for extrapancreatic SPN. The preoperative misdiagnosis also highlights the importance of accurate diagnosis and the development of appropriate treatment strategies for liver masses.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Induction chemotherapy plus re-irradiation versus re-irradiation alone in locally recurrent nasopharyngeal carcinoma: A model-based analysis.

OBJECTIVE: To investigate the role of additional induction chemotherapy (IC) prior to re-irradiation in locally recurrent nasopharyngeal carcinoma (lrNPC). METHODS: A total of 480 patients from three cancer treatment centers who received re-irradiation between 2012 and 2020 were retrospectively analyzed. Overall survival (OS) was determined using the Kaplan-Meier method and compared with log-rank method. Inverse probability of treatment weighting (IPTW) was performed to match the patients in pairwise treatment groups. Multivariate analysis using the Cox proportional hazards regression method identified predictors of OS. The risk stratification model was defined by the risk score calculated with the sum of coefficients. RESULTS: In the entire cohort, the addition of IC was associated with similar OS compared with radiotherapy alone (P = 0.58) or with concomitant chemoradiation (P = 0.76). A risk stratification model was constructed and validated based on significant prognostic factors (coefficient) including male (0.6), age ≥ 60 years (0.9), volume of recurrence gross tumor volume ≥ 16 cc (0.7), and lactate dehydrogenase (LDH)-ratio ≥ 0.5 (0.4). In the intermediate-risk group (sum of coefficient: 0.9---1.6), patients with IC plus re-irradiation had a significantly better OS than those who received re-irradiation (P = 0.03). After adjustments for several potentially confounding variables with IPTW, survival benefit of IC was also observed (P = 0.031). However, no significant difference in OS for the additional IC prior to re-irradiation was demonstrated in the low- (sum of coefficient: <0.9) and high-risk group (sum of coefficient: > 1.6). CONCLUSION: Additional IC prior to re-irradiation was associated with improved OS in the intermediate-risk group of lrNPC, whereas there was no difference for the low-risk and high-risk group. Prospective validation is required to validate these findings.

Stealth microplastics pollutants: Toxicological evaluation of polyethylene terephthalate-based glitters on the microalga Desmodesmus sp. and its color effect.

Polyethylene terephthalate-based glitters (PET glitters) are a potential source of primary microplastics in the environment. However, the bioeffects of PET glitters and the associated leachates remain largely unknown. In this study, we investigated the individual and combined toxicity of five colors (silver, black, red, green, and blue) of PET glitters and their corresponding leachates on the cellular responses of Desmodesmus sp. The results indicated that the photosynthesis of Desmodesmus sp. could be partly affected by PET glitters through the shading effect, but not that of growth. Conversely, the leachates of red and green PET glitters significantly inhibited the growth of the microalga, suggesting a higher risk associated with additives leached from these colors of PET glitters. Furthermore, the adverse effects of the co-occurrence of PET glitters and leachates were closely related to oxidative stress responses in the microalgal cells, along with a color effect, which could be mainly attributed to variations in the composition and abundance of toxic additives in different colors of PET glitters. Overall, our findings provide insights into the ecological risks posed by glitters in aquatic environments and emphasize the importance of considering color factors in assessing microplastics toxicity.

[Clinical characteristics and efficacy of oropharyngeal carcinoma with secondary primary tumor].

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.

[Research progress in diagnosis and treatment of HPV-associated oropharyngeal squamous cell carcinoma].

Oropharyngeal carcinoma is one of the most common malignant tumors of head and neck. In recent years, the incidence of Human papilloma virus-associated oropharyngeal squamous cell carcinoma（HPV-OPSCC） has been increasing year by year. With the advancement of minimally invasive surgical techniques, the wide application of intensity modulated radiation therapy, and the demand of patients for organ function protection and higher quality of life, the unique biological behavior and better prognosis of HPV-OPSCC have led to the exploration of a series of attenuated treatment modes. This article reviews the diagnosis and treatment status of oropharyngeal cancer and related research progress based on relevant reports.

Toxicity interaction of polystyrene nanoplastics with sulfamethoxazole on the microalgae Chlamydomonas reinhardtii: A closer look at effect of light availability.

The coexistence of nanoplastics and antibiotics in the aquatic environment has raised a complicated risk for ecosystems and human health. How the environmental factors e.g., light, regulate the interaction between nanoplastics and antibiotics and the resulting combined toxicity is poorly understood. Here, we investigated the individual and combined toxicity of polystyrene nanoplastics (nPS, 100 mg L1) and sulfamethoxazole (SMX, 2.5 and 10 mg L-1) toward the microalgae Chlamydomonas reinhardtii under low (LL, 16 µmol m-2·s-1), normal (NL, 40 µmol m-2·s-1), and high light (HL, 150 µmol m-2·s-1) in terms of cellular responses. Results indicated that the joint toxicity of nPS and SMX commonly exhibited a strong antagonistic/mitigative effect under LL/NL at 24 h, and under NL at 72 h. nPS could adsorb more SMX under LL/NL at 24 h (1.90/1.33 mg g-1) and under NL at 72 h (1.01 mg g-1), thereby alleviating SMX toxicity to C. reinhardtii. However, the self-toxicity of nPS had a negative influence on the degree of antagonism between nPS and SMX. The experimental results coupled with computational chemistry further revealed that the adsorption capacity of SMX on nPS was stimulated by low pH under LL/NL at 24 h (∼7.5), while by less co-existing saline ions (0.83 ppt) and algae-derived dissolved organic matter (9.04 mg L-1) under NL at 72 h. nPS toxicity that was responsible for the toxic action modes was mainly attributed to the shading effect induced by hetero-aggregation and hindrance of light transmittance (>60%), as well as being regulated by additives leaching (0.49-1.07 mg L-1) and oxidative stress. Overall, these findings provided a critical basis for the risk assessment and management of multiple pollutants in the complex natural environment.

Purification efficiency of Pyropia-processing wastewater and microalgal biomass production by the combination of Chlorella sp. C2 cultivated at different culture temperatures and chitosan.

To elucidate the impacts of culture temperature on nutrient removal efficiency of Pyropia-processing wastewater (PPW) and microalgal biomass production, Chlorella sp. C2 was employed and cultivated in raw PPW under different temperatures. Results showed that, after incubating for 7 days, higher biomass (0.50 g/L) and total lipids (21.84 %) were attained at 35 °C. The maximal chemical oxygen demand (COD), phycobiliprotein, total nitrogen and total phosphorus removal rates were observed at 30-35 °C and separately reached 62.41 %, 92.61 %, 92.19 % and 98.33 %. Interestingly, COD removal efficiencies of Chlorella cells, cultivated for 3, 5 and 7 days at 30-35 °C, 15-25 °C and 10 °C respectively, could reach >75 % with assistance from 60-80 mg/L chitosan. Meanwhile, the clarification efficiency of chitosan on algal cells reached >95 %. It suggests that Chlorella strain cultured at altered temperatures could efficiently remove PPW nutrients assisted by moderate chitosan, simultaneously achieving the rapid harvest of microalgae.

The Periparturient Gut Microbiota's Modifications in Shaziling Sows concerning Bile Acids.

Shaziling pigs, as a native Chinese breed, have been classified as a fatty liver model. As the core of the whole pig farm, the sow's organism health is especially important, especially in the perinatal period; however, there are few reports on the perinatal intestinal microbiology and bile acid metabolism of Shaziling pig sows. The purpose of this research was to investigate the alterations in bile acids and gut microbiota of sows that occur throughout the perinatal period. Forty-two sows were selected for their uniformity of body conditions and were given the same diet. Fecal samples were collected for 16srDNA sequencing and bile acid targeted metabolome detection in four stages (3 days before delivery, 3 days after delivery, 7 days after delivery and 21 days after delivery). As revealed by the results, there were statistically significant variations in bile acids among the four stages, with the concentration of bile acids identified by SZL-4 being substantially greater than that of the other three groups (p < 0.05). When compared to the other three groups (p < 0.05), SZL-2 had considerably lower Shannon, Simpson and Chao 1 indices, and exhibited a statistically significant difference in ß-diversity. SZL-2 samples included a greater proportion of Proteobacteria than SZL-3 and SZL-4 samples; however, SZL-2 samples contained a smaller proportion of spirochetes than SZL-3 and SZL-4 samples. To a large extent, lactic acid bacteria predominated in the SZL-2 samples. The LEfSe analysis showed that the relative abundances of Lachnospiraceae_XPB1014_group, Christensenellaceae_R_7_group, Clostridium, Collinsella, Turicibacter, and Mollicutes_RF39_unclassified were the main differential bacteria in the SZL-1 swine fecal samples and the Eubacterium__coprostanoligenes_group in sow fecal samples from SZL-2. The relative abundance of Bacteroides, UBA1819, Enterococcus, Erysipelatoclostridium, and Butyricimonas in SZL-3 and SZL-4 Streptococcus, Coriobacteriaceae_unclassified, Prevotellaceae_UCG_001, Streptomyces, and Ochrobactrum in SZL-3. g_Collinsella was significantly and positively correlated with vast majority bile acids, and the g_Lachnospiraceae_XPB1014_group with GCDCA and GHDCA into positive correlations. Simultaneously, g_Streptococcus, g_Bacteroides, and g_UBA1819 inversely correlated with bile acid, accounting for the great bulk of the difference. In conclusion, there is an evident correlation between bile acids and gut microbiota in the perinatal period of Shaziling sows. Additionally, the discovery of distinct bacteria associated to lipid metabolism gives a reference for ameliorating perinatal body lipid metabolism disorder of sows through gut microbiota.

Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

Flv3A facilitates O2 photoreduction and affects H2 photoproduction independently of Flv1A in diazotrophic Anabaena filaments.

The model heterocyst-forming filamentous cyanobacterium Anabaena sp. PCC 7120 (Anabaena) is a typical example of a multicellular organism capable of simultaneously performing oxygenic photosynthesis in vegetative cells and O2 -sensitive N2 -fixation inside heterocysts. The flavodiiron proteins have been shown to participate in photoprotection of photosynthesis by driving excess electrons to O2 (a Mehler-like reaction). Here, we performed a phenotypic and biophysical characterization of Anabaena mutants impaired in vegetative-specific Flv1A and Flv3A in order to address their physiological relevance in the bioenergetic processes occurring in diazotrophic Anabaena under variable CO2 conditions. We demonstrate that both Flv1A and Flv3A are required for proper induction of the Mehler-like reaction upon a sudden increase in light intensity, which is likely important for the activation of carbon-concentrating mechanisms and CO2 fixation. Under ambient CO2 diazotrophic conditions, Flv3A is responsible for moderate O2 photoreduction, independently of Flv1A, but only in the presence of Flv2 and Flv4. Strikingly, the lack of Flv3A resulted in strong downregulation of the heterocyst-specific uptake hydrogenase, which led to enhanced H2 photoproduction under both oxic and micro-oxic conditions. These results reveal a novel regulatory network between the Mehler-like reaction and the diazotrophic metabolism, which is of great interest for future biotechnological applications.

Light availability modulates the responses of the microalgae Desmodesmus sp. to micron-sized polyvinyl chloride microplastics.

The vertical movement of large-size and high-density MPs in the water column is usually along with dynamic changes in light intensity. However, whether the change in light availability affects the bioeffects of MPs on surrounding microalgae is currently unknown. This study investigated the effects of micron-sized polyvinyl chloride (mPVC, 143.5 µm) microplastics, alone and in combination with light intensity (from 7.5 to 162.5 µmol·m-2·s-1) on the growth and physiology of Desmodesmus sp. Although mPVC did not impact microalgal growth under optimal light (40 and 93.8 µmol·m-2·s-1), it could induce a no-contact shading effect, thereby significantly affecting the physiology of Desmodesmus sp. The growth of Desmodesmus sp. exposed to mPVC was enhanced under a high light intensity of 162.5 µmol·m-2·s-1 which can induce growth inhibition but was retarded when under a light inadequacy condition (20 µmol·m-2·s-1), along with a dose-dependent effect. Significantly, the photosynthesis of Desmodesmus sp. was a highly sensitive metabolic pathway to mPVC stress and largely influenced by the plastic particles under different light conditions. Additionally, mPVC modulated the energy metabolism strategy of Desmodesmus sp., depending on exposure dose and external light availability. Our findings provided a critical basis for the risk assessment of MPs in fluctuating light conditions.

Prognostic value of neutrophil-to-lymphocyte ratio for patients with triple-negative breast cancer: A meta-analysis.

We aimed to evaluate the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in patients with triple-negative breast cancer (TNBC). We searched the PubMed Database, Cochrane Library, Web of science, and Embase. Overall survival (OS), disease-free survival (DFS), and hazard ratio (HR) were the endpoints of the study. Eleven studies involving 2355 patients with TNBC were included in this meta-analysis. Among them, 10 studies involving 2069 patients with TNBC investigated the role of NLR in predicting OS; elevated NLR was associated with poor prognosis (hazard ratio [HR]: 2.48, 95% confidence interval [CI]: 2.03-3.03, P < 0.001). Ten studies involving 2054 patients with TNBC explored the role of NLR in predicting DFS; elevated NLR was associated with a significantly worse prognosis with a pooled HR of 2.20 (95% CI: 1.88-2.58, P < 001). This meta-analysis suggests that patients with TNBC who have a higher NLR have poorer prognoses. As a clinical parameter that we can easily obtain, NLR might be a potential predictor of patients' survival, and may be useful for physicians' treatment decisions.

Delineation of neck node levels for patients with locally advanced supraglottic cancer receiving radical intensity-modulated radiotherapy: a cross-sectional study in Mainland China.

Background: To survey the diversity of clinical target volumes (CTVs) for locally advanced supraglottic cancer (LA-SGC) with radical radiotherapy in mainland China. Methods: Radiation oncologists from 30 provinces and four representative cases (T2N1, T3N2b, T4N0, T4N2c) were included. Results: High risk (HR)-CTV included involved and the lower adjacent level was followed by most physicians (n = 160, 97.6%). In the N0-1 stage, whether contralateral levels II-III should be included in HR- or low risk (LR)-CTV was controversial. In the N2 stage, the bilateral levels II-IVb were included in LR-CTV (75-92.5% agreement). Levels Ib, V or VIb were included in CTV requiring certain conditions. Conclusion: Involved and lower adjacent levels were as HR-CTV. Whether bilateral levels II-IV are included in HR- or LR-CTV remain controversial.

Low temperature combined with high inoculum density improves alpha-linolenic acid production and biochemical characteristics of Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii grows fast and is rich in polyunsaturated fatty acids. To explore whether the alpha-linolenic acid (ALA) content can be further enhanced, the cultures were incubated under different culture temperatures, light intensities and inoculum densities. Results showed that temperature exhibited more great impact on ALA synthesis of C. reinhardtii than light intensity and inoculum size. The changes of light intensity and inoculum size displayed non-significant effects on ALA content. The optimal ALA proportion in cells was obtained under the condition of 10 °C, 50 µE/m2/s and 5% inoculum density, which reached âˆ¼ 39%.The augmented initial inoculum density could markedly improve the biomass of C. reinhardtii under 10 °C. The maximum ALA productivity (16.42 mg/L/d) was gained under 10 °C coupled with 25% inoculum size, where higher intracellular sugar and protein yield were observed. These results suggest C. reinhardtii would be an alternative feedstock for the industrial production of ALA.