Hydrologic Connectivity Regulates Riverine N2O Sources and Dynamics.

Indirect nitrous oxide (N2O) emissions from streams and rivers are a poorly constrained term in the global N2O budget. Current models of riverine N2O emissions place a strong focus on denitrification in groundwater and riverine environments as a dominant source of riverine N2O, but do not explicitly consider direct N2O input from terrestrial ecosystems. Here, we combine N2O isotope measurements and spatial stream network modeling to show that terrestrial-aquatic interactions, driven by changing hydrologic connectivity, control the sources and dynamics of riverine N2O in a mesoscale river network within the U.S. Corn Belt. We find that N2O produced from nitrification constituted a substantial fraction (i.e., >30%) of riverine N2O across the entire river network. The delivery of soil-produced N2O to streams was identified as a key mechanism for the high nitrification contribution and potentially accounted for more than 40% of the total riverine emission. This revealed large terrestrial N2O input implies an important climate-N2O feedback mechanism that may enhance riverine N2O emissions under a wetter and warmer climate. Inadequate representation of hydrologic connectivity in observations and modeling of riverine N2O emissions may result in significant underestimations.

The contribution of wetland plant litter to soil carbon pool: Decomposition rates and priming effects.

Plant litter input is an important driver of soil/sediment organic carbon (SOC) turnover. A large number of studies have targeted litter-derived C input tracing at a global level. However, little is known about how litter carbon (C) input via various plant tissues affects SOC accumulation and mineralization. Here, we conducted laboratory incubation to investigate the effects of leaf litter and stem litter input on SOC dynamics using the natural 13C isotope technique. A 122-day laboratory incubation period showed that litter input facilitated SOC accumulation. Leaf and stem litter inputs increased soil total organic carbon content by 37.6% and 15.5%, respectively. Leaf litter input had a higher contribution to SOC accumulation than stem litter input. Throughout the incubation period, the δ13C values of stem litter and leaf litter increased by 1.5‰ and 3.3‰, respectively, while δ13CO2 derived from stem litter and δ13CO2 derived from leaf litter decreased by 4.2‰ and 6.1‰, respectively, suggesting that the magnitude of δ13C in litter and δ13CO2 shifts varied, depending on litter tissues. The cumulative CO2-C emissions of leaf litter input treatments were 27.56%-42.47% higher than those of the stem litter input treatments, and thus leaf litter input promoted SOC mineralization more than stem litter input. Moreover, the proportion of increased CO2-C emissions to cumulative CO2-C emissions (57.18%-92.12%) was greater than the proportion of litter C input to total C (18.7%-36.8%), indicating that litter input could stimulate native SOC mineralization, which offsets litter-derived C in the soil. Overall, litter input caused a net increase in SOC accumulation, but it also accelerated the loss of native SOC. These findings provide a reliable basis for assessing SOC stability and net C sink capacity in wetlands.

Treated wastewater and weak removal mechanisms enhance nitrate pollution in metropolitan rivers.

The focus of urban water environment renovation has shifted to high nitrate (NO3-) load. Nitrate input and nitrogen conversion are responsible for the continuous increase in nitrate levels in urban rivers. This study utilized nitrate stable isotopes (δ15N-NO3- and δ18O-NO3-) to investigate NO3- sources and transformation processes in Suzhou Creek, located in Shanghai. The results demonstrated that NO3- was the most common form of dissolved inorganic nitrogen (DIN), accounting for 66 ± 14% of total DIN with a mean value of 1.86 ± 0.85 mg L-1. The δ15N-NO3- and δ18O-NO3- values ranged from 5.72 to 12.42‰ (mean value: 8.38 ± 1.54‰) and -5.01 to 10.39‰ (mean value: 0.58 ± 1.76‰), respectively. Based on isotopic evidence, the river received a significant amount of nitrate through direct exogenous input and sewage ammonium nitrification, while nitrate removal (denitrification) was insignificant, resulting in nitrate accumulation. Analysis using the MixSIAR model revealed that treated wastewater (68.3 ± 9.7%), soil nitrogen (15.7 ± 4.8%) and nitrogen fertilizer (15.5 ± 4.9%) were the main sources of NO3- in rivers. Despite the fact that Shanghai's urban domestic sewage recovery rate has reached 92%, reducing nitrate concentrations in treated wastewater is crucial for addressing nitrogen pollution in urban rivers. Additional efforts are needed to upgrade urban sewage treatment during low flow periods and/or in the main stream, and to control non-point sources of nitrate, such as soil nitrogen and nitrogen fertilizer, during high flow periods and/or tributaries. This research provides insights into NO3- sources and transformations, and serves as a scientific basis for controlling NO3- in urban rivers.

Ebullition Controls on CH4 Emissions in an Urban, Eutrophic River: A Potential Time-Scale Bias in Determining the Aquatic CH4 Flux.

Rivers and streams contribute significant quantities of methane (CH4) to the atmosphere. However, there is a lack of CH4 flux and ebullitive (bubble) emission data from urban rivers, which might lead to large underestimations of global aquatic CH4 emissions. Here, we conducted high-frequency surveys using the boundary layer model (BLM) supplemented with floating chambers (FCs) and bubble traps to investigate the seasonal and diurnal variability in CH4 emissions in a eutrophic urban river and to evaluate whether the contribution of bubbles is important. We found that ebullition contributed nearly 99% of CH4 emissions and varied on hourly to seasonal time scales, ranging from 0.83 to 230 mmol m-2 d-1, although diffusive emissions and CH4 concentrations in bubbles did not exhibit temporal variability. Ebullitive CH4 emissions presented high temperature sensitivity (r = 0.6 and p < 0.01) in this urban river, and eutrophication might have triggered this high temperature sensitivity. The ebullitive CH4 flux is more likely to be underestimated at low temperatures because capturing the bubble flux is more difficult, given the low frequency of ebullition events. This study suggests that future ebullition measurements on longer time scales are needed to accurately quantify the CH4 budgets of eutrophic urban rivers.

Both sampling seasonality and geographic origin contribute significantly to variations in raw milk microbiota, but sampling seasonality is the more determining factor.

Accurately profiling and characterizing factors shaping raw milk microbiota would provide practical information for detecting microbial contamination and unusual changes in milk. The current work was an observational study aiming to profile the microbiota of raw milk collected across wide geographic regions in China in different seasons and to investigate the contribution of geographical, seasonal, and environmental factors in shaping the raw milk microbiota. A total of 355 raw cow milk samples from healthy Holsteins and 41 environmental samples (farm soil and surface of milking room floor) were collected from 5 dairy farms in 5 Chinese provinces (namely, Daqing in Heilongjiang province, Jiaozuo in Henan province, Qingyuan in Guangdong province, Suqian in Jiangsu province, and Yinchuan in Ningxia Hui Autonomous Region) in January, May, and September 2018. The microbial communities in raw milk and farm environmental samples were determined using the PacBio small-molecule real-time circular consensus sequencing, which generated high-fidelity microbiota profiles based on full-length 16S rRNA genes; such technology was advantageous in producing accurate species-level information. Our results showed that both seasonality and sampling region were significant factors influencing the milk microbiota; however, the raw milk microbiota was highly diverse according to seasonality, and sampling region was the less determining factor. The wide variation in raw milk microbial communities between samples made it difficult to define a representative species-level core milk microbiota. Nevertheless, 3 most universal milk-associated species were identified: Lactococcus lactis, Enhydrobacter aerosaccus, and Acinetobacter lwoffii, which were consistently detected in 99%, 95%, and 94% of all analyzed milk samples, respectively (n = 355). The top taxa accounting for the overall seasonal microbiota variation were Bacillus (Bacillus cereus, Bacillus flexus, Bacillus safensis), Lactococcus (Lactococcus lactis, Lactococcus piscium, Lactococcus raffinolactis), Lactobacillus (Lactobacillus helveticus, Lactobacillus delbrueckii), Lactiplantibacillus plantarum, Streptococcus agalactiae, Enhydrobacter aerosaccus, Pseudomonas fragi, and Psychrobacter cibarius. Unlike the milk microbiota, the environmental microbiota did not exhibit obvious pattern of seasonal or geographic variation. However, this study was limited by the relatively low number and types of environmental samples, making it statistically not meaningful to perform further correlation analysis between the milk and environmental microbiota. Nevertheless, this study generated novel information on raw milk microbiota across wide geographic regions of China and found that seasonality was more significant in shaping the raw milk microbiota compared with geographic origin.

Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases.

Human cytomegalovirus (HCMV) belongs to the ß-herpesvirus family, which is transmitted in almost every part of the world and is carried by more than 90% of the general population. Increasing evidence indicates that HCMV infection triggers numerous diseases by disrupting the normal physiological activity of host cells, particularly apoptosis. Apoptosis disorder plays a key role in the initiation and development of multiple diseases. However, the relationship and molecular mechanism of HCMV-related diseases and apoptosis have not yet been systematically summarized. This review aims to summarize the role of apoptosis in HCMV-related diseases and provide an insight into the molecular mechanism of apoptosis induced by HCMV infection. We summarize the literature on HCMV-related diseases and suggest novel strategies for HCMV treatment by regulating apoptosis.

The involvement of post-translational modifications in cardiovascular pathologies: Focus on SUMOylation, neddylation, succinylation, and prenylation.

Cardiovascular disease (CVD) is one of the most threatening diseases to human health and life, and the number of patients is increasing year by year. Thus, it is of great significance to study the pathogenesis, prevention and treatment of CVDs. The occurrence and development of CVDs involve dynamic, complex and delicate intracellular processes and the pathogenesis is not entirely clear. In contrast to genetic mutations, most of the protein post-translational modifications (PTMs) are reversible, and can affect the activity, stability, subcellular localization, protein-protein interaction etc., of the substrate targets, emerging as key mediators of a number of CVD progression. Under pathological conditions, the PTMs undergo aberrant balances which cause changes of the substrate target proteins in expression level, localization and capacity to activate downstream signaling pathways. Therefore, new approaches can be created aiming to correct the abnormal PTM alterations in treating CVDs. This review summarizes some of the more recent advances in PTMs, focusing on SUMOylation, neddylation, succinylation, and prenylation, and the effect of these modifications on cardiovascular function and progression, which may provide potential targets for future therapeutics.

Baicalein inhibits mitochondrial apoptosis induced by oxidative stress in cardiomyocytes by stabilizing MARCH5 expression.

Abnormal mitochondrial fission and mitophagy participate in the pathogenesis of many cardiovascular diseases. Baicalein is a key active component in the roots of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. It has been reported that baicalein can resist cardiotoxicity induced by several stress, but the mechanisms of baicalein operate in the protection of cardiomyocytes need to be researched further. Here we report that baicalein can promote cell survival under oxidative stress by up-regulating the expression level of MARCH5 in cardiomyocytes. Pre-treatment cells or mice with baicalein can stabilize the expression of MARCH5, which plays a crucial role in the regulation of mitochondrial network and mitophagy. Overexpressed MARCH5 is able to against H2 O2 and ischaemia/reperfusion (I/R) stress by suppressing mitochondrial fission and enhancing mitophagy, and then attenuate cells apoptosis. Altogether, our present study investigated that baicalein exerts a protective effect through regulating KLF4-MARCH5-Drp1 pathway, our research also provided a novel theoretical basis for the clinical application of baicalein.

A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis.

Liver injury is the early stage of liver disease, which is caused by multiple factors. Baicalein has shown extensive bioactivity. But whether baicalein has a protective effect on liver injury has not been reported thus far. In this study, we aim to investigate the protective effects of baicalein on liver injury induced by oxidative stress. H2O2 and CCl4 were employed to establish liver injury models in vivo and in vitro, respectively. The protective effect of baicalein on oxidative stress-induced liver injury was evaluated by detecting the mitochondrial dynamics, the level of autophagy and apoptosis, the histopathology of liver, the indicators of liver function, and the level of oxidative stress in vitro and in vivo. March5 is the key regulator during liver injury induced by oxidative stress. March5 can ubiquitinate Drp1 and promote Drp1 degradation, then maintain the homeostasis of mitochondrial dynamics, keep the balance of autophagy, and reduce apoptosis. Baicalein is able to effectively reduce liver injury; it can contribute to the expression of March5 by regulating KLF4 during liver injury. These results indicate that baicalein plays a key role in salvaging liver from injury induced by oxidative stress via regulating the KLF4-March5-Drp1 signal pathway.

Correction to: A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis.

The original version of this article unfortunately contains errors in methods and figures. In methods, animal experiments part: "2 ml/kg" and "after two days" were described incorrectly which were actually "4 ml/kg" and "after eight days" respectively.

Multiyear Measurements on Δ17O of Stream Nitrate Indicate High Nitrate Production in a Temperate Forest.

Nitrification is a crucial step in ecosystem nitrogen (N) cycling, but scaling up from plot-based measurements of gross nitrification to catchments is difficult. Here, we employed a newly developed method in which the oxygen isotope anomaly (Δ17O) of nitrate (NO3-) is used as a natural tracer to quantify in situ catchment-scale gross nitrification rate (GNR) for a temperate forest from 2014 to 2017 in northeastern China. The annual GNR ranged from 71 to 120 kg N ha-1 yr-1 (average 94 ± 10 kg N ha-1 yr-1) over the 4 years in this forest. This result and high stream NO3- loss (4.2-8.9 kg N ha-1 yr-1) suggest that the forested catchment may have been N-saturated. At the catchment scale, the total N output of 10.7 kg N ha-1 yr-1, via leaching and gaseous losses, accounts for 56% of the N input from bulk precipitation (19.2 kg N ha-1 yr-1). This result indicates that the forested catchment is still retaining a large fraction of N from atmospheric deposition. Our study suggests that estimating in situ catchment-scale GNR over several years when combined with other conventional flux estimates can facilitate the understanding of N biogeochemical cycling and changes in the ecosystem N status.

Fermented milk containing Lactobacillus casei Zhang and Bifidobacterium animalis ssp. lactis V9 alleviated constipation symptoms through regulation of intestinal microbiota, inflammation, and metabolic pathways.

Studies suggest that probiotics and fermented milk can improve defecation in constipated patients. However, the mechanism of fermented milk containing probiotics on constipation remains poorly understood. Volunteers with chronic constipation symptoms were recruited and given 200 g/d of fermented milk containing Lactobacillus casei Zhang and Bifidobacterium animalis ssp. lactis V9 (PFM) for 4 wk. Clinical symptoms, cytokines, metagenomics, and metabolomics were evaluated in constipated participants before and after PFM intervention. After PFM intervention, we observed significant improvement of constipation symptoms. In the serum samples, the anti-inflammatory cytokine IL-10 increased and the proinflammatory cytokine C-reactive protein and lipopolysaccharides decreased. Metagenomics results showed that the increase of B. animalis was correlated with an increase in defecation frequency. Fatty acid biosynthesis and bile acid biosynthesis in stool samples as well as carnitine shuttle, vitamin E metabolism, and ascorbate and aldarate metabolism were identified as significantly altered metabolic pathways. Acylcarnitine, located on the carnitine shuttle pathway, had a significantly positive correlation with defecation frequency. It was speculated that PFM may contribute to alleviating constipation symptoms through 3 potential mechanisms: fine-tuning gastrointestinal microbiota, fighting inflammation, and regulating metabolic pathways.

Mitochondrial protein 18 is a positive apoptotic regulator in cardiomyocytes under oxidative stress.

Accumulation of reactive oxygen species is a common phenomenon in cardiac stress conditions, for instance, coronary artery disease, aging-related cardiovascular abnormalities, and exposure to cardiac stressors such as hydrogen peroxide (H2O2). Mitochondrial protein 18 (Mtp18) is a novel mitochondrial inner membrane protein, shown to involve in the regulation of mitochondrial dynamics. Although Mtp18 is abundant in cardiac muscles, its role in cardiac apoptosis remains elusive. The present study aimed to detect the role of Mtp18 in H2O2-induced mitochondrial fission and apoptosis in cardiomyocytes. We studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. We then analyzed mitochondrial morphological dynamics with MitoTracker Red staining; apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) and cell death detection assays; and protein expression with immunoblotting. Here, we observed that Mtp18 could regulate oxidative stress- mediated mitochondrial fission and apoptosis in cardiac myocytes. Mechanistically, we found that Mtp8 induced mitochondrial fission and apoptosis by enhancing dynamin-related protein 1 (Drp1) accumulation. Conversely, knockdown of Mtp18 interfered with Drp1-associated mitochondrial fission and subsequent activation of apoptosis in both HL-1 cells and primary cardiomyocytes. However, overexpression of Mtp18 alone was not sufficient to execute apoptosis when Drp1 was minimally expressed, suggesting that Mtp18 and Drp1 are interdependent in apoptotic cascade. Together, these data highlight the role of Mtp18 in cardiac apoptosis and provide a novel therapeutic insight to minimize cardiomyocyte loss via targetting mitochondrial dynamics.

Bacterial diversity and community structure in Chongqing radish paocai brines revealed using PacBio single-molecule real-time sequencing technology.

BACKGROUND: Traditional Chongqing radish paocai fermented with aged brine is considered to have the most intense flavor and authentic taste. Eight 'Yanzhi' (red, RRPB group) and 'Chunbulao' (white, WRPB) radish paocai brine samples were collected from Chongqing peasant households, and the diversity and community structures of bacteria present in these brines were determined using PacBio single-molecule real-time sequencing of their full-length 16S rRNA genes. RESULTS: In total, 30 phyla, 218 genera, and 306 species were identified from the RRPB group, with 20 phyla, 261 genera, and 420 species present in the WRPB group. Obvious differences in bacterial profiles between the RRPB and WRPB groups were found, with the bacterial diversity of the WRPB group shown to be greater than that of the RRPB group. This study revealed several characteristics of the bacteria composition, including the predominance of heterofermentative lactic acid bacteria, the species diversity of genus Pseudomonas, and the presence of three opportunistic pathogenic species. CONCLUSION: This study provides detailed information on the bacterial diversity and community structure of Chongqing radish paocai brine samples, and suggests it may be necessary to analyze paocai brine for potential sources of bacterial contamination and take appropriate measures to exclude any pathogenic species. © 2018 Society of Chemical Industry.

Bacterial microbiota of Kazakhstan cheese revealed by single molecule real time (SMRT) sequencing and its comparison with Belgian, Kalmykian and Italian artisanal cheeses.

BACKGROUND: In Kazakhstan, traditional artisanal cheeses have a long history and are widely consumed. The unique characteristics of local artisanal cheeses are almost completely preserved. However, their microbial communities have rarely been reported. The current study firstly generated the Single Molecule, Real-Time (SMRT) sequencing bacterial diversity profiles of 6 traditional artisanal cheese samples of Kazakhstan origin, followed by comparatively analyzed the microbiota composition between the current dataset and those from cheeses originated from Belgium, Russian Republic of Kalmykia (Kalmykia) and Italy. RESULTS: Across the Kazakhstan cheese samples, a total of 238 bacterial species belonging to 14 phyla and 140 genera were identified. Lactococcus lactis (28.93%), Lactobacillus helveticus (26.43%), Streptococcus thermophilus (12.18%) and Lactobacillus delbrueckii (12.15%) were the dominant bacterial species for these samples. To further evaluate the cheese bacterial diversity of Kazakhstan cheeses in comparison with those from other geographic origins, 16S rRNA datasets of 36 artisanal cheeses from Belgium, Russian Republic of Kalmykia (Kalmykia) and Italy were retrieved from public databases. The cheese bacterial microbiota communities were largely different across sample origins. By principal coordinate analysis (PCoA) and multivariate analysis of variance (MANOVA), the structure of the Kazakhstan artisanal cheese samples was found to be different from those of the other geographic origins. Furthermore, the redundancy analysis (RDA) identified 16 bacterial OTUs as the key variables responsible for such microbiota structural difference. CONCLUSION: Our results together suggest that the diversity of bacterial communities in different groups is stratified by geographic region. This study does not only provide novel information on the bacterial microbiota of traditional artisanal cheese of Kazakhstan at species level, but also interesting insights into the bacterial diversity of artisanal cheeses of various geographical origins.

Efficacy of passive sampler collection for atmospheric NO2 isotopes under simulated environmental conditions.

RATIONALE: Nitrogen oxides or NOx (NOx = NO + NO2 ) play an important role in air quality, atmospheric chemistry, and climate. The isotopic compositions of anthropogenic and natural NO2 sources are wide-ranging, and they can be used to constrain sources of ambient NO2 and associated atmospheric deposition of nitrogen compounds. While passive sample collection of NO2 isotopes has been used in field studies to determine NOx source influences on atmospheric deposition, this approach has not been evaluated for accuracy or precision under different environmental conditions. METHODS: The efficacy of NO2 passive sampler collection for NO2 isotopes was evaluated under varied temperature and relative humidity (RH) conditions in a dynamic flux chamber. The precision and accuracy of the filter NO2 collection as nitrite (NO2- ) for isotopic analysis were determined using a reference NO2 gas tank and through inter-calibration with a modified EPA Method 7. The bacterial denitrifer method was used to convert 20 µM of collected NO2- or nitrate (NO3- ) into N2 O and was carried out on an Isoprime continuous flow isotope ratio mass spectrometer. RESULTS: δ15 N-NO2 values determined from passive NO2 collection, in conditions of 11-34 °C, 1-78% RH, have an overall accuracy and precision of ±2.1 ‰, and individual run precision of ±0.6 ‰. δ18 O-NO2 values obtained from passive NO2 sampler collection, under the same conditions, have an overall precision of ± 1.3 ‰. CONCLUSIONS: Suitable conditions for passive sampler collection of NO2 isotopes are in environments ranging from 11 to 34 °C and 1 to 78% RH. The passive NO2 isotope measurement technique provides an accurate method to determine variations in atmospheric δ15 N-NO2 values and a precise method for determining atmospheric δ18 O-NO2 values. The ability to measure NO2 isotopes over spatial gradients at the same temporal resolution provides a unique perspective on the extent and seasonality of fluctuations in atmospheric NO2 isotopic compositions. Copyright © 2017 John Wiley & Sons, Ltd.

Novel Method for Nitrogen Isotopic Analysis of Soil-Emitted Nitric Oxide.

The global inventory of NOx (NOx = NO + NO2) emissions is poorly constrained, with a large portion of the uncertainty attributed to soil NO emissions that result from soil abiotic and microbial processes. While natural abundance stable N isotopes (δ15N) in various soil N-containing compounds have proven to be a robust tracer of soil N cycling, soil δ15N-NO is rarely quantified due to the measurement difficulties. Here, we present a new method that collects soil-emitted NO through NO conversion to NO2 in excess ozone (O3) and subsequent NO2 collection in a 20% triethanolamine (TEA) solution as nitrite and nitrate for δ15N analysis using the denitrifier method. The precision and accuracy of the method were quantified through repeated collection of an analytical NO tank and intercalibration with a modified EPA NOx collection method. The results show that the efficiency of NO conversion to NO2 and subsequent NO2 collection in the TEA solution is >98% under a variety of controlled conditions. The method precision (1σ) and accuracy across the entire analytical procedure are ±1.1‰. We report the first analyses of soil δ15N-NO (-59.8‰ to -23.4‰) from wetting-induced NO pulses at both laboratory and field scales that have important implications for understanding soil NO dynamics.

Hepatocyte growth factor-induced differentiation of bone mesenchymal stem cells toward hepatocyte-like cells occurs through nuclear factor-kappa B signaling in vitro.

Hepatocyte growth factor (HGF) is multifaceted cytokine that regulates proliferation, differentiation, morphology, and motility within numerous stem cells. More recently, HGF has been reported to induce the differentiation of bone mesenchymal stem cells (BMSCs) into mature hepatocytes, but the underlying biochemical and molecular signaling is largely unknown. We isolated BMSC from the bone marrow of rats, which were then cultured and exposed to HGF for 15 days. We subsequently assayed these cells for liver functionality and markers, and blocked NF-кB signaling at various stages of the pathway. The present results demonstrate that HGF induces the differentiation of BMSCs toward hepatocyte-like cells through the NF-кB signaling. More specifically, HGF upregulated the translocation of NF-кB to the nucleus.

Developing innovative strategies of tumor­infiltrating lymphocyte therapy for tumor treatment.

Cancer is the main cause of global mortality, and thus far, effective therapeutic strategies for cancer treatment are in high demand. Adoptive transfer of tumor­infiltrating lymphocytes (TILs) represents a promising avenue in immunotherapy for the management of malignancies. The clinical safety and efficacy of TIL­based therapy have been established through numerous rigorous clinical trials. However, the efficacy of TIL infusion in inducing an anti­tumor response is limited to a subset of clinical patients with cancer. Therefore, there is an urgent need to develop innovative strategies aimed at enhancing the effectiveness of TIL­based therapy. In the present review, the developmental history of TIL­based therapy was systematically summarized and analyzed, while also presenting a unique perspective on enhancing the multi­dimensional anti­tumor capabilities of TILs. The insight and conclusions presented in this review may contribute to improving the efficacy of TIL­based therapy and expediting its development.

Effect of examining lymph nodes count on mortality risk in resected T1 non-small-cell lung cancer.

OBJECTIVES: This study aims to estimate the effect of the examined lymph node count (ELNC) on the cancer-related mortality risk and non-cancer-related mortality risk in patients with resected T1 non-small-cell lung cancer (NSCLC). METHODS: Patients diagnosed as primary T1 NSCLC between 2000 and 2017 were extracted from the Surveillance, Epidemiology and End Results database. Patients were divided into 2 groups according to the ELNC cutoff value, which was calculated based on overall survival outcomes. Propensity score matching was used to equalize the differences in baseline characteristics between groups. RESULTS: A total of 38 242 resected T1 NSCLC patients were extracted from the database with the ELNC cutoff value of 8. After propensity score matching, 27 676 patients were included in this study. Examining ≥8 ELNC was associated with a more accurate assessment of lymph node (LN) metastasis and significantly improving the prognosis. These trends remained consistent in subgroup analysis by histology type. In competing risk mode, examining ≥8 LNs could significantly reduce the risk of death from lung cancer, risk of death from chronic obstructive pulmonary disease, and risk of death from cardiac diseases. In the subgroup analysis, these trends were consistent. CONCLUSIONS: Given the mortality risk associated with lung cancer, chronic obstructive pulmonary disease, and cardiac diseases, at least 8 LNs should be examined in surgery for T1 NSCLC.