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The study of agricultural non-point source pollution (ANNSP) patterns and driving mechanisms is crucial for regional ecological management. This paper evaluates the sources of ANNSP in the Huang-Huai-Hai Plain for the years 2000, 2010, and 2020 using the source list method. Additionally, nitrogen source data for the InVEST model were supplemented and adjusted, and the nitrogen output load and proportions derived in farmland from both methods were compared. The temporal and spatial distribution of nitrogen emission intensity was analyzed based on InVEST model outputs. Key source areas were identified through hotspot analysis, and spatial driving factors were examined using geodetector. Key findings reveal: 1) While the source list method estimated a higher nitrogen output load, both methods concurred on the proportion of agricultural nitrogen. The main sources of nitrogen input were overuse of fertilizer and livestock breeding. 2) Over this period, nitrogen emission intensity declined, exhibiting a distinct spatial pattern of “northwest low, southeast high.” 3) The extent of critical source areas underwent a dynamic shift, initially contracting before expanding. 4) Rainfall emerged as the primary driver of spatial variability in agricultural TN emission intensity. These insights offer critical reference points for achieving efficient ANNSP management in the Huang-Huai-Hai Plain.

A reasonable ecological security pattern can improve landscape connectivity, promote biological circulation, maintain ecological processes, and improve regional ecosystem service functions and human well-being. Accordingly, systematically and scientifically analyzing the spatiotemporal evolution characteristics of the regional ecological security pattern has essential theoretical and practical significance. This research proposed that the analysis framework of the ecological security pattern should include a complete system composed of ecological sources, resistance surfaces, and corridors. Thus, this research uses the ecological network method to systematically analyze the spatiotemporal evolution characteristics of the ecological security pattern in the Qinba–Dabie intersection zone in China, a complete natural ecological unit across administrative regions, from 2000 to 2020. Results revealed the following: (1) The distribution change law of the ecological sources in the study area was consistent with the distribution change law of their centrality. (2) In the northeast of the study area, the disappearance of the small ecological sources, which play a stepping stone role, led to a longer length and a weaker centrality of ecological corridors. (3) The resistance surface in the study area showed an overall growth trend, while the ecological corridor network showed an overall deterioration trend. Based on the results, this research suggests that the systematic analysis and targeted protection of ecological sources are the basis for maintaining the ecological security pattern, and targeted improvement of ecological resistance surface is the key to improving the ecological security pattern. Therefore, measures such as the protection of core ecological sources, the rational layout of ecological sources as stepping stones, and the improvement of resistance values at ecological key points should be paid attention to in the future.

IntroductionIn order to explore the correlation between discharge readiness and Harris score or self-care ability of patients undergoing total hip arthroplasty (THA) based on the enhanced recovery after surgery (ERAS) concept. We carried out this single center retrospective study.MethodsWe enrolled 331 patients who underwent THA. These patients were divided into the higher score group and the lower score group according to median discharge readiness score. After the baseline data of these patients were compared, the effect factors of discharge readiness of these patients was analyzed through univariate and multivariate logistic regression analyses and mixed effects models.ResultsThe results demonstrated that there was a correlation between discharge readiness and changes in Harris score 30 days after discharge (compared with that before surgery) in these patients. Besides, the Harris score and self-care ability 30 days after discharge were higher than those at the time of discharge. In addition, patients in the higher score group exhibited a higher Harris score compared with those in the lower score group. From the evaluation at different time points after discharge, there was a significant difference in the Harris score between both groups.DiscussionIt can be inferred that the discharge readiness of patients undergoing THA was correlated with the Harris score but not with the self-care ability. These results are expected to provide guidance for the physical and mental recovery of patients undergoing total hip replacement under the ERAS concept. Furthermore, these findings may contribute to higher diagnosis, treatment, and nursing levels of orthopedic medical staff.

Influenza A virus (IAV) is a negative-sense single-stranded RNA virus that causes acute lung injury and acute respiratory distress syndrome, posing a serious threat to both animal and human health. N6-methyladenosine (m6A), a prevalent and abundant post-transcriptional methylation of RNA in eukaryotes, plays a crucial regulatory role in IAV infection by altering viral RNA and cellular transcripts to affect viral infection and the host immune response. This review focuses on the molecular mechanisms underlying m6A modification and its regulatory function in the context of IAV infection and the host immune response. This will provide a better understanding of virus–host interactions and offer insights into potential anti-IAV strategies.

BackgroundSerum creatinine is a prognostic marker for various conditions, but its significance of spontaneous subarachnoid hemorrhage is still poorly understood. This study aims to elucidate the correlation between admission serum creatinine (sCr) levels and all-cause mortality within 30 days among individuals affected by non-traumatic subarachnoid hemorrhage (SAH).MethodsThis cohort study included 672 non-traumatic SAH adults. It utilized data from the MIMIC-IV database from 2008 to 2019. The patients’ first-time serum creatinine was recorded. Subsequently, an examination of the 30-day all-cause mortality was conducted. Employing a multiple logistic regression model, a nomogram was constructed, while the association between sCr and 30-day all-cause mortality was evaluated using Kaplan–Meier survival curves. The calibration curve was employed to assess the model’s performance, while subgroup analysis was employed to examine the impact of additional complications and medication therapy on outcomes.ResultsA total of 672 patients diagnosed with non-traumatic subarachnoid hemorrhage were included in the study. The mortality rate within this timeframe was found to be 24.7%. Multiple logistic regression analysis revealed that sCr served as an independent prognostic indicator for all-cause mortality within 30 days of admission for SAH patients [OR: 2(1.18–3.41); p = 0.01]. A comprehensive model was constructed, incorporating age, sCr, white blood cell count (WBC), glucose, anion gap, and partial thromboplastin time (PTT), resulting in a prediction model with an AUC value of 0.806 (95% CI: 0.768, 0.843), while the AUC for the test set is 0.821 (95% CI: 0.777–0.865).ConclusionCreatinine emerges as a significant biomarker, closely associated with heightened in-hospital mortality in individuals suffering from SAH.

The pathogenic mechanisms of bacterial infections and resultant sepsis are partly attributed to dysregulated inflammatory responses sustained by some late-acting mediators including the procathepsin-L (pCTS-L). It was entirely unknown whether any compounds of the U.S. Drug Collection could suppress pCTS-L-induced inflammation, and pharmacologically be exploited into possible therapies. Here, we demonstrated that a macrophage cell-based screening of a U.S. Drug Collection of 1360 compounds resulted in the identification of progesterone (PRO) as an inhibitor of pCTS-L-mediated production of several chemokines [e.g., Epithelial Neutrophil-Activating Peptide (ENA-78), Monocyte Chemoattractant Protein-1 (MCP-1) or MCP-3] and cytokines [e.g., Interleukin-10 (IL-10) or Tumor Necrosis Factor (TNF)] in primary human peripheral blood mononuclear cells (PBMCs). In vivo, these PRO-entrapping 2,6-dimethal-β-cyclodextrin (DM-β-CD) nanoparticles (containing 1.35 mg/kg PRO and 14.65 mg/kg DM-β-CD) significantly increased animal survival in both male (from 30% to 70%, n = 20, P = 0.041) and female (from 50% to 80%, n = 30, P = 0.026) mice even when they were initially administered at 24 h post the onset of sepsis. This protective effect was associated with a reduction of sepsis-triggered accumulation of three surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF) by 40%; Macrophage Inflammatory Protein-2 (MIP-2) by 45%; and Soluble Tumor Necrosis Factor Receptor I (sTNFRI) by 80%]. Surface Plasmon Resonance (SPR) analysis revealed a strong interaction between PRO and pCTS-L (KD = 78.2 ± 33.7 nM), which was paralleled with a positive correlation between serum PRO concentration and serum pCTS-L level (ρ = 0.56, P = 0.0009) or disease severity (Sequential Organ Failure Assessment, SOFA; ρ = 0.64, P = 0.0001) score in septic patients. Our observations support a promising opportunity to explore DM-β-CD nanoparticles entrapping lipophilic drugs as possible therapies for clinical sepsis.

Background and purposeNeutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with six-month outcomes.MethodsRetrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR.ResultsA total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively.ConclusionNLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings.

ObjectiveThis study aimed to retrospectively investigate the use of oral contrast-enhanced ultrasonography (O-CEUS) in assessing the thickness of the gastric wall for gastric cancer (GC) screening and to establish screening strategies for GC with different risk stratifications based on the gastric wall thickness.MethodsFrom January 2015 to March 2020, people who underwent O-CEUS at the Physical Examination Center of our hospital with at least three years of follow-up were included in this study. The thickness of the gastric wall measured by O-CEUS was divided into three groups using 6 mm and 9 mm as cutoff values. The occurrence of GC in each group was observed. The imaging and clinical information of these populations were recorded and analyzed. Kaplan–Meier survival analysis and Cox’s proportional hazards regression were performed to calculate the risk of GC occurrence.ResultsA total of 4,047 people were finally included in this study. During the follow-up period, GC occurred in 7 individuals (incidence rate 0.17%). Among them, according to the thickness of the gastric wall, one case occurred in Group A (< 6 mm), two cases occurred in Group B (6-9 mm), and four cases occurred in Group C (>9mm). Based on Kaplan–Meier survival analysis, the curves of the three groups were significantly different (P < 0.01). The risk of GC occurrence in Group C and Group B were higher than that in Group A (4.76E+2-fold and 1.50E+2-fold).ConclusionO-CEUS is a convenient, economical, safe, and noninvasive screening method for GC. Measuring the thickness of the gastric wall is helpful to predict the risk of GC occurrence according to our stratification screening system.

ObjectiveThe lactate/albumin ratio (LAR) has been used as a novel prognostic indicator for aneurysmal subarachnoid hemorrhage, traumatic brain injury, sepsis, heart failure, and acute respiratory failure. However, its potential in predicting all-cause mortality in patients with ischemic stroke (IS) has not been evaluated. Therefore, this study aimed to elucidate the correlation between LAR and 28-day all-cause mortality in IS patients without reperfusion therapy.MethodsThis retrospective cohort study used data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.0) database. It included 568 IS adult patients admitted to the intensive care unit (ICU). The correlation between LAR and ICU 28-day all-cause mortality rate was analyzed using multiple COX regression analysis and Kaplan–Meier survival analysis. Restricted cubic spline (RCS) curves were used to assess the relationship between LAR and 28-day mortality. In addition, a subgroup analysis was performed to investigate the impact of other influencing factors on outcomes. The primary outcome was the ability of LAR to predict 28-day mortality in IS patients.ResultsAmong the 568 patients with IS, 370 survived (survival group) and 198 died (non-survival group) within 28 days of admission (mortality rate: 34.9%). A multivariate COX regression analysis indicated that LAR was an independent predictor of all-cause mortality within 28 days after admission for patients with IS (hazard ratio: 1.32; 95% confidence interval: 1.03–1.68; P = 0.025). We constructed a model that included LAR, age, race, sex, white blood cell count, Sequential Organ Failure Assessment (SOFA) score, and anion gap (AG) and established a prediction model with an area under the curve (AUC) value of 71.5% (95% confidence interval: 67.1%−75.8%). The optimal cutoff value of LAR that separated the survival group and the non-survival group based on the Youden index was 0.55. The Kaplan-Meier survival curves plotted using this critical value showed that patients with LAR ≥ 0.55 had a significantly higher 28-day all-cause mortality rate than patients with LAR < 0.55 (P = 0.0083).ConclusionLAR can serve as an independent predictor of all-cause mortality within 28 days after admission for patients with IS.

The aim of this study was to explore the characteristics of non-point source pollution of nitrogen (N) and phosphorus (P) under the background of climate and land use in Shandong Province. First, using the InVEST NDR module in the model, N and P non-point source pollution in 2010 and 2020 in Shandong Province were simulated; then, based on precipitation data under three different global climate models (MRI-ESM-0, GFDL-ESM4, and Ec-Earth3) and two Shared Socioeconomic Pathways (SSP245 and SSP585), land use data under two Shared Socioeconomic Pathways (SSP245 and SSP585) were used to simulate and predict the non-point source pollution of N and P in Shandong Province in 2030. The results showed the following: (1) On the time scale, the output load and total output of N and P decreased during 2010–2020, while the output load and total output of N and P increased during 2020–2030. (2) On the spatial scale, the spatial distribution of N and P output loads in 2010, 2020, and 2030 is roughly the same, being “low in the northwest and high in the southeast”. (3) Different climate scenarios have a great influence on N and P output load and total output, and the N and P pollution in the SSP585 scenario is more serious. The total output of N and P did not change much in different climate models, while the spatial distribution of the output load of N and P varied significantly, indicating that different climate models had a greater impact on the spatial distribution of the output load of N and P. (4) The overall cold hot spot pattern of nitrogen and phosphorus pollution in Shandong Province is stable, basically showing a “band + cluster + scatter” distribution pattern; the hot spot area in the central and southern region of Shandong Province changes little regardless of the model, the northwest is basically a cold spot area, and the nitrogen and phosphorus hot spot area under the SSP245 scenario in Ec-Earth3 model had the least amount of change. According to research results, combined with the actual situation of Shandong Province, it is hoped that it can provide theoretical basis for the prevention and control of non-point source pollution in Shandong Province in the future.

Under the influence of climate change and human activities, the intra-annual distribution characteristics of streamflow have changed, directly affecting the exploitation of water resources and the health of ecosystems. The trend-free pre-whitening Mann-Kendall (TFPW-MK) test method, concentration degree and concentration period, and Bernaola-Galvan (BG) segmentation algorithm were applied to analyze variation trend, intra-annual distribution characteristics, and abrupt year of streamflow. Then, the monthly water storage and monthly actual evaporation of the source area of the Lancang River (SALR) were calculated by the monthly ABCD model. Finally, the contributions of different factors to runoff variability at multiple time scales were quantified using the seasonal-scale Budyko hypothesis approach. The results showed that: (1) The runoff revealed a significant upward trend on the annual scale. Runoff exhibited a significant upward trend in January, October and November, and runoff in other months and seasons exhibited an insignificant upward trend. (2) The intra-annual distribution characteristics of runoff in the SALR showed an obvious “Single-peak type“ distribution, reaching a maximum in July and August. (3) The year of sudden change in streamflow was 2008. (4) The contribution of climate change and human activities to the annual runoff change was 83.3% and 16.7%, respectively. The degree of influence of climate change on runoff change was ranked as spring (96.8%), autumn (85.3%), winter (82.2%) and summer (58.2%). The order of impact of human activity on runoff change was summer (41.8%), winter (17.8%), autumn (14.7%), spring (3.2%).

tRNA-derived small RNAs (tsRNAs) represent a novel category of small non-coding RNAs and serve as a new regulator of gene expression at both transcriptional and post-transcriptional levels. Growing evidence indicates that tsRNAs can be induced by diverse stimuli and regulate stress-responsive target genes, allowing plants to adapt to unfavorable environments. Here, we discuss the latest developments about the biogenesis and classification of tsRNAs and highlight the expression regulation and potential function of tsRNAs in plant biotic and abiotic stress responses. Of note, we also collect useful bioinformatics tools and resources for tsRNAs study in plants. Finally, we propose current limitations and future directions for plant tsRNAs research. These recent discoveries have refined our understanding of whether and how tsRNAs enhance plant stress tolerance.

The Lancang River Basin (LCRB) is the largest international river in Southeast Asia, and any change in its streamflow, i.e., due to the ecological environment and runoff, may lead to disputes between countries to a certain extent. However, the impact of vegetation change on streamflow in the LCRB needs to be clarified. To assess the impact of vegetation change on streamflow in the LCRB, the functional relationship between Budyko parameter (ω) and Normalized Difference Vegetation Index (NDVI) was first computed for constructing a modified Budyko formula. Finally, we quantitatively estimated the influence of different factors on streamflow variation in the LCRB using the modified Budyko formula and the elastic coefficient method. The conclusions were as follows: (1) A sudden change in streamflow at the Yunjinghong hydrological station appeared in 2005; (2) Budyko parameter (ω) has a good linear functional relationship with NDVI in the LCRB (p < 0.01); ND (3) vegetation variation played the largest driving force behind streamflow variation in the LCRB, accounting for 34.47%. The contribution rates of precipitation, potential evaporation, and anthropogenic activities on streamflow variation from 1982 to 2015 were 16.83, 17.61, and 31.09%, respectively.

The medicinal plant Cannabis sativa L. (C. sativa) accumulates plant cytotoxic but medicinally important cannabinoids in glandular trichomes and flowers of female plants. Although the major biosynthetic pathway of cannabinoids has been revealed, their transportation mechanism is still unknown. Multidrug and toxic compound extrusion proteins (MATEs) can transport plant metabolites, ions and phytohormones intra and inter-cellularly. MATEs could have the potential to translocate cannabinoids or their synthetic intermediates to cellular compartment, thus protecting them from unwanted modifications and cytotoxicity. In this study, we performed a genome-wide identification and expression analysis of Cannabis sativa MATEs (CsMATEs) and revealed 42 CsMATEs that were classified phylogenetically into four conserved subfamilies. Forty-two CsMATEs were unevenly distributed on 10 chromosomes, with 50% CsMATEs were physically adjacent to at least one another CsMATEs and 83% CsMATEs localized on plasma membrane. Tandem duplication is the major evolutionary driving force for CsMATEs expansion. Real-time quantitative PCR revealed CsMATE23, CsMATE28 and CsMATE34 mainly expressed in flower, whereas CsMATE17 and CsMATE27 showed strong transcription in root. Light responsive cis-acting element was most abundant in promoters of CsMATE23, CsMATE28 and CsMATE34. Finally, the contents of cannabinoids and corresponding biosynthetic intermediates as well as expressions of CsMATE28 and CsMATE34 were determined under UV-B treatment, among which strong correlation was found. Our results indicates that CsMATEs might involve in biosynthesis of cannabinoids and has the potential to be used in heterologous production of cannabinoids.

Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10B-labeled BPA (10B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague–Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue.

The marginalization of farmland is the progression of farmland utilization from high to low net profit, and the abandonment of farmland is its extreme form, and cultivated land marginalization is an important problem that needs to be properly controlled in the process of economic and social development. In this paper, cultivated land was extracted from the land database and evaluated from the aspects of natural suitability, farming convenience and farming opportunity cost, etc. By setting the combined weight of the three evaluation results and stacking them with the forest land extracted from remote sensing images, the potential risk range of cultivated land marginalization was identified, and an empirical study was carried out in Mengjin County, Henan Province. Results showed that: 1) the natural factors of cultivated land were stable and not easy to change, and the natural suitability was the basic condition that affected the marginalization of cultivated land. There was a spatial correlation between the natural suitability of cultivated land and the cultivation convenience, and the risk of marginalization of cultivated land with poor natural suitability and inconvenient cultivation conditions was higher. 2) The high-opportunity cost areas are mainly distributed in the inner suburbs of cities, and the cultivated land in this area is highly likely to be adjusted to high-benefit agriculture such as flowers, vegetables and sightseeing agriculture. Therefore, the risk of abandonment of cultivated land is less. 3) Adjusting cultivated land with poor natural suitability and inconvenient tillage conditions to forest land is conducive to the restoration of regional fragile ecology. Comprehensive improvement of cultivated land with high natural suitability but inconvenient tillage is an important way to delay the marginalization of cultivated land. This study provides a new idea for the formulation of farmland marginalization prevention and control policies at county level.

The Belt and Road Initiative (BRI) significantly contributes to the world economy. However, the central part of the Belt and Road (B&R) is located in fragile ecological zones that are arid, semi-arid, or sub-humid. Using the entropy method, the economic-social-natural ecological niches and their coupling coordination during 2007–2019 along B&R’s 11 countries were explored along with regional differences and spatiotemporal characteristics. The economic-social-natural ecological niches were low, with a fluctuating upward trend. Additionally, the average annual growth rate of the synthesis ecological niche dramatically improved after the BRI. Further, the BRI facilitated inter-country trade and promoted the economic ecological niche. However, the BRI marginally affected the social ecological position, possibly because the social ecological niche was high pre-BRI. The natural ecological niche showed a negative growth after the BRI. Further, the coupling coordination of economic-social ecological niche and natural ecological niche showed an upward trend, transforming from severe discoordination to advanced coordination. Although BRI promoted advanced coordination, it did not affect internal categories. Policy recommendations for sustainable development in China-ASEAN Free Trade Area were provided. This study can assist policymakers to balance economic-social development and environmental protection.

BackgroundThe status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC.MethodsThis study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR)ResultsThere was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patientsConclusionsThe CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.

BackgroundLarge hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment.MethodsThis study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup.ResultsIn CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients.ConclusionsPreoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.

Background and AimTo investigate the effect of preoperative circulation tumor cells (CTCs) on postoperative recurrence and overall survival prognosis of pancreatic head cancer after pancreaticoduodenectomy (PD).MethodsFrom March 2014 to January 2018, 73 patients with pancreatic head cancer underwent radical resection (R0) in Zhongshan People's Hospital. CTCs in peripheral blood of patients with pancreatic head cancer were detected by “Cyttel” method before PD. Seventy-three patients were divided into positive and negative groups according to the positive criteria. To explore the relationship between the clinical data of CTCs and disease-free survival (DFS) and overall survival (OS). Cox proportional hazards model was used to analyzing the risk factors affecting the postoperative recurrence and the survival prognosis of patients.Results41 patients (56.2%) were in the CTC-positive group. Preoperative CTCs were correlated with tumor vascular invasion, CA199 level and postoperative liver metastasis (P < 0.05). Preoperative CTC-positive, lymph node metastasis, vascular invasion, and nerve invasion were independent risk factors for DFS (P < 0.05). Preoperative CTC-positive, tumor diameter > 2 cm and vascular invasion were independent risk factors for OS of patients (P < 0.05).ConclusionThe detection of CTCs before PD is an important factor affecting the DFS and OS of pancreatic head cancer, which is significant in guiding clinical work.

Due to strict spectral band requirements, the three-band (TB) chlorophyll-a concentration (Cchla) estimation algorithm cannot be applied to GOCI image, which has great potential in frequently monitoring inland complex waters. In this study, the TB algorithm was expanded and applied to GOCI data. The GOCI TB algorithm was subsequently calibrated using an in-situ dataset which contains 281 samples collected from 17 inland lakes in China between 2013 and 2020. MERIS TB and GOCI band ratio (BR) models were selected as comparisons to assess the proposed model. The results showed that the proposed GOCI TB model has similar accuracy with MERIS TB model and overperformed GOCI BR model. The root mean square error (RMSE) of the GOCI TB, MERIS TB, and GOCI BR algorithms are 14.212 μg/L, 12.096 μg/L, and 20.504 μg/L, respectively. The mean absolute percentage error (MAPE) (when Cchla is larger than 10 μg/L) of the three models were 0.377, 0.250, and 0.453, respectively. Similar conclusion could be drawn from a match-up dataset containing 40 samples. Finally, a simulation experiment was carried out to analyze the robustness of the models under various total suspended matter concentration (CTSM) conditions. Both the in-situ validation and simulation experiment indicated that the GOCI TB factor could effectively eliminate the optical influence of CTSM. Furthermore, the broader spectral range requirement of GOCI TB model made it proper for many other multispectral sensors such as Sentinel two Multispectral Instrument (S2 MSI), Moderate Resolution Imaging Spectroradiometer (MODIS) (onboard the Terra/Aqua satellite), and Visible Infrared Imaging Radiometer Suite (VIIRS) (onboard the National Polar-orbiting Partnership satellite). Compared with the GOCI BR algorithm, the GOCI TB algorithm has stronger stability, better accuracy, and greater potential in practice.

BackgroundHepatic ischemia and reperfusion (I/R) injury is commonly associated with surgical liver resection or transplantation, and represents a major cause of liver damage and graft failure. Currently, there are no effective therapies to prevent hepatic I/R injury other than ischemic preconditioning and some preventative strategies. Previously, we have revealed the anti-inflammatory activity of a sweat gland-derived peptide, dermcidin (DCD), in macrophage/monocyte cultures. Here, we sought to explore its therapeutic potential and protective mechanisms in a murine model of hepatic I/R.MethodsMale C57BL/6 mice were subjected to hepatic ischemia by clamping the hepatic artery and portal vein for 60 min, which was then removed to initiate reperfusion. At the beginning of reperfusion, 0.2 ml saline control or solution of DCD (0.5 mg/kg BW) or DCD-C34S analog (0.25 or 0.5 mg/kg BW) containing a Cys (C)→Ser (S) substitution at residue 34 was injected via the internal jugular vein. For survival experiments, mice were subjected to additional resection to remove non-ischemic liver lobes, and animal survival was monitored for 10 days. For mechanistic studies, blood and tissue samples were collected at 24 h after the onset of reperfusion, and subjected to measurements of various markers of inflammation and tissue injury by real-time RT-PCR, immunoassays, and histological analysis.ResultsRecombinant DCD or DCD-C34S analog conferred a significant protection against lethal hepatic I/R when given intravenously at the beginning of reperfusion. This protection was associated with a significant reduction in hepatic injury, neutrophilic CXC chemokine (Mip-2) expression, neutrophil infiltration, and associated inflammation. Furthermore, the administration of DCD also resulted in a significant attenuation of remote lung inflammatory injury. Mechanistically, DCD interacted with epidermal growth factor receptor (EGFR), a key regulator of liver inflammation, and significantly inhibited hepatic I/R-induced phosphorylation of EGFR as well as a downstream signaling molecule, protein kinase B (AKT). The suppression of EGFR expression by transducing Egfr-specific shRNA plasmid into macrophages abrogated the DCD-mediated inhibition of nitric oxide (NO) production induced by a damage-associated molecular pattern (DAMP), cold-inducible RNA-binding protein, CIRP.ConclusionsThe present study suggests that human DCD and its analog may be developed as novel therapeutics to attenuate hepatic I/R-induced inflammatory injury possibly by impairing EGFR signaling.

The coronavirus disease 2019 (COVID-19) pandemic has greatly disrupted the normal treatment of patients with liver cancer and increased their risk of death. The weight of therapeutic safety was significantly amplified for decision-making to minimize the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, the safety and effectiveness of carbon ion radiotherapy (CIRT) for unresectable liver cancer (ULC) were evaluated, and Chinese experiences were shared to solve the predicament of ULC treatment caused by SARS-CoV-2. Worldwide studies were collected to evaluate CIRT for ULC as the world has become a community due to the COVID-19 pandemic. We not only searched five international databases including the Cochrane Library, Web of Science, PubMed, Embase, and Scopus but also performed supplementary retrieval with other sources. Chinese experiences of fighting against COVID-19 were introduced based on the advancements of CIRT in China and a prospective clinical trial of CIRT for treating ULC. A total of 19 studies involving 813 patients with ULC were included in the systematic review. The qualitative synthetic evaluation showed that compared with transarterial chemoembolization (TACE), CIRT could achieve superior overall survival, local control, and relative hepatic protection. The systematic results indicated that non-invasive CIRT could significantly minimize harms to patients with ULC and concurrently obtain superior anti-cancer effectiveness. According to the Chinese experience, CIRT allows telemedicine within the hospital (TMIH) to keep a sufficient person-to-person physical distance in the whole process of treatment for ULC, which is significant for cutting off the transmission route of SARS-CoV-2. Additionally, CIRT could maximize the utilization rate of hospitalization and outpatient care (UHO). Collectively, CIRT for ULC patients not only allows TMIH and the maximized UHO but also has the compatible advantages of safety and effectiveness. Therefore, CIRT should be identified as the optimal strategy for treating appropriate ULC when we need to minimize the risk of SARS-CoV-2 infection and to improve the capacity of medical service in the context of the unprecedented COVID-19 crisis.

Histone deacetylases (HDACs) play crucial roles nearly in all aspects of plant biology, including stress responses, development and growth, and regulation of secondary metabolite biosynthesis. The molecular functions of HDACs have been explored in depth in Arabidopsis thaliana, while little research has been reported in the medicinal plant Cannabis sativa L. Here, we excavated 14 CsHDAC genes of C. sativa L that were divided into three relatively conserved subfamilies, including RPD3/HDA1 (10 genes), SIR2 (2 genes), and HD2 (2 genes). Genes associated with the biosynthesis of bioactive constituents were identified by combining the distribution of cannabinoids with the expression pattern of HDAC genes in various organs. Using qRT-PCR and transcription group analysis, we verified the expression of candidate genes in different tissues. We found that the histone inhibitor Trichostatin A (TSA) affected the expression of key genes in the cannabinoid metabolism pathway and the accumulation of synthetic precursors, which indirectly indicates that histone inhibitor may regulate the synthesis of active substances in C. sativa L.

To moderate fast neutrons produced by accelerator to appropriate therapeutic energies for boron neutron capture therapy (BNCT), beam shaping assembly (BSA) is required definitely. In this work, based on a model of 2.5 MeV/30 mA proton accelerator, the Monte Carlo simulation software MCNPX was employed to design multi-terminal BSAs. All parameters for both the thermal and epithermal neutron beams at the exit ports of the designed BSAs meet the treatment recommendation values proposed by the International Atomic Energy Agency (IAEA). The clinical parameters of the thermal and epithermal neutron beams were also calculated for clinical indication consideration.

The development of abdominal aortic aneurysm (AAA) is attributed to psychological and physical factors. Topiramate, which is an agonist of the GABAA receptor, makes contributions to neuronal disease and is partially involved in immune regulation, may be effective upon abdominal aortic aneurysm progression. We used experimental abdominal aortic aneurysm models: Angiotensin II (Ang II)–induced ApoE−/− male mice (Ang II/APOE model) in our study. In the Ang II/APOE model, all mice (n=64) were divided into four groups: sham group (PBS treatment), control group (Ang II treatment), low-dose group (Ang II + low-dose topiramate, 3 mg/day per mouse), and high-dose group (Ang II + high-dose topiramate, 6 mg/day per mouse). All treatments began on the day after surgery. Moreover, collected tissues and cultured cell were used for histology and biochemical examination. In vitro, the effects of topiramate on bone marrow-derived macrophage stimulated by LPS were investigated. Our data implied that topiramate treatment significantly promoted macrophages preservation and conversion of M1 to M2 macrophage phenotypes in vivo and in vitro. Accordingly, proinflammatory activities mediated by the M1 macrophages were decreased and the repair process mediated by M2 macrophages was enhanced. The low-dose and high-dose groups had abdominal aortic aneurysm incidences of 50% and 37.5%, respectively, compared with 75% in the control group. Topiramate, a promising drug for the psychological disease, that target neuro-immune-induced macrophage polarization may attenuate experimental abdominal aortic aneurysm progression.

Objective: The lactate/albumin ratio (LAR) has been used as a novel prognostic indicator for aneurysmal subarachnoid hemorrhage, traumatic brain injury, sepsis, heart failure, and acute respiratory failure. However, its potential in predicting all-cause mortality in patients with ischemic stroke (IS) has not been evaluated. Therefore, this study aimed to elucidate the correlation between LAR and 28-day all-cause mortality in IS patients without reperfusion therapy. Methods: This retrospective cohort study used data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.0) database. It included 568 IS adult patients admitted to the intensive care unit (ICU). The correlation between LAR and ICU 28-day all-cause mortality rate was analyzed using multiple COX regression analysis and Kaplan-Meier survival analysis. Restricted cubic spline (RCS) curves were used to assess the relationship between LAR and 28-day mortality. In addition, a subgroup analysis was performed to investigate the impact of other influencing factors on outcomes. The primary outcome was the ability of LAR to predict 28-day mortality in IS patients. Results: Among the 568 patients with IS, 370 survived (survival group) and 198 died (non-survival group) within 28 days of admission (mortality rate: 34.9%). A multivariate COX regression analysis indicated that LAR was an independent predictor of all-cause mortality within 28 days after admission for patients with IS (hazard ratio: 1.32; 95% confidence interval: 1.03-1.68; P = 0.025). We constructed a model that included LAR, age, race, sex, white blood cell count, Sequential Organ Failure Assessment (SOFA) score, and anion gap (AG) and established a prediction model with an area under the curve (AUC) value of 71.5% (95% confidence interval: 67.1%-75.8%). The optimal cuto value of LAR that separated the survival group and the non-survival group based on the Youden index was 0.55. The Kaplan-Meier survival curves plotted using this critical value showed that patients with LAR ≥ 0.55 had a significantly higher 28-day all-cause mortality rate than patients with LAR < 0.55 (P = 0.0083). Conclusion: LAR can serve as an independent predictor of all-cause mortality within 28 days after admission for patients with IS. [ABSTRACT FROM AUTHOR]

Background and purpose: Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with sixmonth outcomes. Methods: Retrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR. Results: A total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively. Conclusion: NLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Rapid, accurate, and quantitative characterization of immune status of patients is of utmost importance for disease diagnosis and prognosis, evaluating efficacy of immunotherapeutics and tailoring drug treatments. Immune status of patients is often dynamic and patient-specific, and such complex heterogeneity has made accurate, real-time measurements of patient immune status challenging in the clinical setting. Recent advances in microfluidics have demonstrated promising applications of the technology for immune monitoring with minimum sample requirements and rapid functional immunophenotyping capability. This review will highlight recent developments of microfluidic platforms that can perform rapid and accurate cellular functional assays on patient immune cells. We will also discuss the future potential of integrated microfluidics to perform rapid, accurate, and sensitive cellular functional assays at a single-cell resolution on different types or subpopulations of immune cells, to provide an unprecedented level of information depth on the distribution of immune cell functionalities. We envision that such microfluidic immunophenotyping tools will allow for comprehensive and systems-level immunomonitoring, unlocking the potential to transform experimental clinical immunology into an information-rich science. [ABSTRACT FROM AUTHOR]