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At present,there are few studies focusing on the effect of negative bias voltage on the corrosion resistance of TiAlN films deposited by arc ion plating.In this paper,TiAlN films were deposited on M2 high speed steel by arc ion plating,and scanning electron microscope (SEM),X-ray diffraction (XRD),electrochemical test and other methods were used to study the influences of negative bias voltage on substrate on the microstructure,surface morphology and corrosion resistance of the as-prepared films.Results showed that the negative bias voltage was an important process parameter affecting the surface morphology of TiAlN films deposited by arc ion plating.A proper negative bias voltage could effectively improve the morphology and compactness of the surface film and reduce the size and number of large molten droplets on the surface.The main phase of TiAlN films was AlTi3N(111),and the films mainly grew along the (111) direction.When the negative bias voltage was increased,a new reaction would occur and a Ti2AlN (100) diffraction peak would appear.With the increase of the negative bias voltage on substrate,the microhardness of the films increased first and then decreased.When the negative bias voltage was 150 V,the microhardness reached the maximum value of 2 725 HV,the relative corrosion rate was the lowest,and the corrosion resistance was the best.

Abstract Background Sevoflurane and propofol are two popular anesthetics used during glioblastoma (GBM) surgery. This investigation compared the molecular subtypes and immune checkpoints of cancer cells following GBM surgery under sevoflurane and propofol anesthesia. Method The expression profile data and clinical information of glioma samples of different grades were downloaded from The Cancer Genome Atlas database. Weighted gene coexpression network analysis was used to identify hub modules and key genes related to glioma grades (G2 and G3). The GEO database (GSE179004) was used to retrieve glioma surgical specimens with different anesthetic gene expression profiles. The differential expression of immune checkpoint genes under various anesthetic settings was examined using the R‐ggplot2. Results Compared to sevoflurane, propofol significantly downregulated SERPINI1 and CAMK2A expression. These are also important factors in glioma grading. Simultaneously, SERPINI1 and CAMK2A were also significantly related to the prognosis of GBM and lower‐grade glioma patients and acted as potential tumor suppressors. In addition, propofol increases the expression of the immune checkpoint molecule, PD‐L1. Conclusions Our study revealed that sevoflurane can more effectively prevent the development of glioma after surgery than propofol, and SERPINI1 can be used as a new independent prognostic factor for glioma.

BackgroundGemcitabine (GEM) is a second-line anticancer drug of choice for some colorectal cancer (CRC) patients, and GEM inability to be commonly available in the clinic due to the lack of clarity of the exact action targets.MethodsThe half maximal inhibitory concentration (IC50) of GEM treatment for 42 CRC cell lines were accessed from the Genomics of Drug sensitivity in Cancer (GDSC) database. High-throughput sequencing data of CRC patients were captured in The Cancer Genome Atlas (TCGA) and Weighted correlation network analysis (WGCNA) was conducted. Pearson correlations were derived for GEM potency-related genes. Differential analysis was conducted in the TCGA cohort to obtain CRC development-related genes (CDRGs), and univariate COX model analysis was performed on CDRGs overlapping with GEM potency-related genes to obtain CDRGs affecting CRC prognosis. Hub genes affecting GEM potency were identified by Spearman correlation.ResultsCALB2 and GPX3 were identified as potential targets for GEM treatment of CRC via prognostic analysis, which we also observed to be elevated with elevated clinical stage in CRC patients. The enhanced expression of CALB2 and GPX3 genes identified in the pathway analysis might inhibit the body metabolism as well as activate immune and inflammation related pathways. In addition, we found that CALB2 and GPX3 could also be considered as prognostic biomarkers in pan-cancer. Finally, we found that CALB2 and GPX3 were remarkably associated with the drug sensitivity of MG-132, Dasatinib, Shikonin, Midostaurin, MS-275, and Z-LNle-CHO, which were expected to be the drugs of choice for GEM combination.ConclusionCALB2 and GPX3 represent prognostic biomarkers for CRC and they might be potential action targets for GEM. Our study offered innovative ideas for GEM administration strategies.

Background: Acute intermittent porphyria (AIP; OMIM#176000) is a genetic disorder that is caused by mutations in the hydroxymethylbilane synthetase (HMBS) gene. This gene encodes the third enzyme in the heme biosynthesis pathway. Human HMBS (hHMBS) contains a 29-residue insert (residues 296-324) at the interface between domains 1 and 3. The function of this insert is currently unknown. In this study, a previously unidentified classical Splicing variant was discovered in the HMBS gene of a female AIP patient from China. The variant was validated through comparison with the patient’s husband and daughter.Methods: Peripheral blood samples were obtained from the patient, the patient’s husband, and their daughter. Gene expression was analyzed using whole exon sequencing and Sanger sequencing. To validate alternative splicing, RNA was extracted from the patient’s peripheral blood and reverse transcribed into cDNA. Aberrant splicing caused by variants was predicted using I-TASSER and PyMOL software to simulate protein structures. Finally, molecular dynamics of the proteins were simulated using the AMBER14sb software.Results: The patient and her daughter have a classical Splicing variant c.912 + 1G>C of the HMBS gene. This variant was not found in the patient’s husband and has not been previously reported in scientific literature. Analysis of the patient’s peripheral blood transcripts revealed that c.912 + 1G>C retained intron 13 and resulted in an exon 13 skipping. Further analysis through homology modelling and molecular dynamics showed that this variant alters the secondary structure of the HMBS protein, leading to functional differences.Conclusion: This research has discovered a new classical Splicing variant c.912 + 1G>C in the HMBS gene that has been identified as pathogenic. This finding not only expands the molecular heterogeneity of AIP but also provides crucial information for genetic diagnosis.

Oxidative disruption of dopaminergic neurons is regarded as a crucial pathogenesis in Parkinson's disease (PD), eventually causing neurodegenerative progression. (-)-Clausenamide (Clau) is an alkaloid isolated from plant Clausena lansium (Lour.), which is well-known as a scavenger of lipid peroxide products and exhibiting neuroprotective activities both in vivo and in vitro, yet with the in-depth molecular mechanism unrevealed. In this study, we evaluated the protective effects and mechanisms of Clau on dopaminergic neuron. Our results showed that Clau directly interacted with the Ser663 of ALOX5, the PKCα-phosphorylation site, and thus prevented the nuclear translocation of ALOX5, which was essential for catalyzing the production of toxic lipids 5-HETE. LC-MS/MS-based phospholipidomics analysis demonstrated that the oxidized membrane lipids were involved in triggering ferroptotic death in dopaminergic neurons. Furthermore, the inhibition of ALOX5 was found to significantly improving behavioral defects in PD mouse model, which was confirmed associated with the effects of attenuating the accumulation of lipid peroxides and neuronal damages. Collectively, our findings provide an attractive strategy for PD therapy by targeting ALOX5 and preventing ferroptosis in dopaminergic neurons.

Objective: Lumbar decompression surgery is an effective treatment for foot drop caused by LDD, but there is controversy about the prognostic factors affecting its efficacy. This study aimed to investigate the factors influencing the surgical outcome of foot drop due to LDD. Methods: A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until May 2022. Two reviewers independently screened the literature, extracted data, and evaluated the quality of the studies based on the inclusion and exclusion criteria. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and STATA 16.0 software was used for meta-analysis. Results: A total of 730 relevant articles were initially identified and 9 articles were finally included in this study for data extraction and mea-analysis. The results of metaanalysis showed that patients with preoperative moderate muscle strength (2-3/5 on the Medical Research Council scale) had better prognosis compared to those with severe muscle weakness. Additionally, the presence of diabetes mellitus was associated with a poorer prognosis for patients with foot drop due to LDD. The OR values (95%CI) of these two factors were 5.882 (4.449, 7.776) and 5.657 (2.094,15.280) respectively. Conclusions: Patients with moderate muscle strength have a better prognosis compared to those with severe muscle weakness. The presence of diabetes mellitus is associated with a poorer prognosis for patients with foot drop due to LDD. These factors should be considered when predicting the surgical outcome of foot drop due to LDD.

Semiconductor lasers, characterized by their high efficiency, small size, low weight, rich wavelength options, and direct electrical drive, have found widespread application in many fields, including military defense, medical aesthetics, industrial processing, and aerospace. The mode characteristics of lasers directly affect their output performance, including output power, beam quality, and spectral linewidth. Therefore, semiconductor lasers with high output power and beam quality are at the forefront of international research in semiconductor laser science. The novel parity–time (PT) symmetry mode-control method provides the ability to selectively modulate longitudinal modes to improve the spectral characteristics of lasers. Recently, it has gathered much attention for transverse modulation, enabling the output of fundamental transverse modes and improving the beam quality of lasers. This study begins with the basic principles of PT symmetry and provides a detailed introduction to the technical solutions and recent developments in single-mode semiconductor lasers based on PT symmetry. We categorize the different modulation methods, analyze their structures, and highlight their performance characteristics. Finally, this paper summarizes the research progress in PT-symmetric lasers and provides prospects for future development.

Background: The noninvasive computed tomography angiography–derived fractional flow reserve (CT-FFR) can be used to diagnose coronary ischemia. With advancements in associated software, the diagnostic capability of CT-FFR may have evolved. This study evaluates the effectiveness of a novel deep learning-based software in predicting coronary ischemia through CT-FFR. Methods: In this prospective study, 138 subjects with suspected or confirmed coronary artery disease were assessed. Following indication of 30%–90% stenosis on coronary computed tomography (CT) angiography, participants underwent invasive coronary angiography and fractional flow reserve (FFR) measurement. The diagnostic performance of the CT-FFR was determined using the FFR as the reference standard. Results: With a threshold of 0.80, the CT-FFR displayed an impressive diagnostic accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and negative predictive value (NPV) of 97.1%, 96.2%, 97.7%, 0.98, 96.2%, and 97.7%, respectively. At a 0.75 threshold, the CT-FFR showed a diagnostic accuracy, sensitivity, specificity, AUC, PPV, and NPV of 84.1%, 78.8%, 85.7%, 0.95, 63.4%, and 92.8%, respectively. The Bland–Altman analysis revealed a direct correlation between the CT-FFR and FFR (p < 0.001), without systematic differences (p = 0.085). Conclusions: The CT-FFR, empowered by novel deep learning software, demonstrates a strong correlation with the FFR, offering high clinical diagnostic accuracy for coronary ischemia. The results underline the potential of modern computational approaches in enhancing noninvasive coronary assessment.

Describing the pore habit of methane hydrate in sediment matrices is essential for understanding natural distribution of methane hydrate, methane trace (transport and solidification) in the hydrate stability zone, physical properties of hydrate-bearing sediments, and the associated influence on potential gas production. Pore habit visualization in natural media at pore scale even with laboratory synthesized cores has been challenging due to the similar densities of methane hydrate from pore liquid. In this work, we used phase-contrast assisted micro-CT with potassium iodine-doped brine to visualize four phases: sand particles, pore fluid, methane hydrate and methane gas. This study visualizes the pore habit of methane hydrate at various stages including during hydrate formation in excess-gas systems, its evolution after brine injection to replace pore fluid, and hydrate formation in excess-water systems. Hydrate tends to adopt round and smooth surfaces when in contact with water while exhibits relatively angular interfaces when in contact with methane gas. Hydrate formation in excess-gas systems results in a partial cementing and partial mineral-coating pore habit, while hydrate in excess-water systems develops mainly as pore-filling, and locally cementing or mineral-coating where big gas pockets exist at the initial state. Pore liquid replacement from methane gas to brine triggers a shift of hydrate pore habit towards pore-filling. Methane hydrate evolution over time produces bigger hydrate particles but with less contact area with sand particles. The effects of hydrate pore habit become less important as hydrate particle size exceeds the pore size. Additionally, hydrate formation could trap residual methane gas and brine as inclusions.

Abstract Background Perfluoroalkyl substances can disrupt hepatic metabolism and may be associated with liver function biomarkers. We examined individual and mixture associations of PFAS on liver function biomarkers in a representative sample of Canadian adults. We explored the potential for effect modification by sex and body mass index, as well as by physical activity level which may attenuate the deleterious effect of PFAS on metabolic disorders. Methods We analyzed data from participants aged 20–74 from the Canadian Health Measures Survey. We used linear regression to examine associations between plasma concentrations of PFOA, PFOS, PFHxS, PFNA, PFDA, and PFUDA on serum concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin. We used quantile g-computation to estimate associations with a PFAS mixture for each simultaneous, one-quartile change in PFAS concentrations. Results Each doubling of PFOA, PFOS, PFHxS, or PFNA concentrations was associated with higher AST, GGT, and ALP concentrations. Each doubling of PFOA concentrations was associated with 16.5% (95%CI: 10.4, 23.0) higher GGT concentrations among adults not meeting Canada’s physical activity guidelines vs. 6.6% (95%CI: -1.6, 15.5) among those meeting these guidelines. Sex and BMI also modified some associations, though to a lesser extent. We did not observe associations between ALT and PFOA (1.2% change; 95%CI: -2.5, 4.9), PFOS (2.2% change; 95%CI: -0.8, 5.3), or PFHxS (1.5% change; 95%CI: -0.4, 3.4). We also did not observe consistent associations for PFDA and PFUDA or with total bilirubin. In quantile g-computation models, each simultaneous one-quartile increase in the PFAS mixture was positively associated with AST (7.5% higher; 95%CI: 4.0, 10.4), GGT (9.7% higher; 95%CI: 1.7, 17.0), and ALP (2.8% higher; 95%CI: 0.5, 5.4). Conclusion Higher plasma concentrations of PFOA, PFOS, PFHxS, and PFNA – both individually and as a mixture – were associated with higher serum concentrations of liver function biomarkers. These results contribute to emerging evidence suggesting that higher levels of physical activity appear to be protective against the hepatotoxic effects of PFOA. This work contributes to a growing body of evidence supporting the hepatotoxic effects of PFAS.

Abstract Objective Whether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified. Methods Consecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale. Results A total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724). Conclusions Preoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Background: The long-term prognosis of patients with hepatocellular carcinoma (HCC) after surgery remains far from satisfactory, especially in patients with microvascular invasion (MVI). This study aimed to evaluate the potential survival benefit from adjuvant lenvatinib for patients with HCC and MVI. Methods: Patients with HCC after curative hepatectomy were reviewed. All patients were divided into 2 groups according to adjuvant lenvatinib. Propensity score matching (PSM) analysis was used to reduce selection bias and make the results more robust. Survival curves are shown by the Kaplan-Meier (K-M) analysis and compared by the Log-rank test. Univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. Results: Of 179 patients enrolled in this study, 43 (24%) patients received adjuvant lenvatinib. After PSM analysis, 31 pairs of patients were enrolled for further analysis. Survival analysis before and after PSM analysis showed a better prognosis in the adjuvant lenvatinib group (all P < .05). The adverse events associated with oral lenvatinib were acceptable. Multivariate Cox regression analysis showed that adjuvant lenvatinib was an independent protective factor for improving overall survival (OS) (hazard ratio [HR] = 0.455, 95% confidence interval [CI] = 0.249-0.831, P = .001) and recurrence-free survival (RFS) (HR = 0.523, 95% CI = 0.308-0.886, P = .016). Conclusions: Postoperative adjuvant targeted therapy can improve the long-term prognosis of patients with HCC and MVI. Therefore, in clinical practice, oral lenvatinib should be recommended for patients with HCC and MVI to decrease tumor recurrence and improve long-term survival.

BackgroundBabao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism.MethodsTo verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS.ResultsWe observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway.ConclusionIn summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.

The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorectal cancer (HACC). In order to explore these characteristics along with their correlation with clinicopathological factors and prognosis in HACC. Samples of 812 CRC patients was collected. After immunohistochemistry (IHC), 59 of 812 were found to be HER2-positive, then 26 of 59 samples were further determined to be HER2 amplification by fluorescence in situ hybridization (FISH). Somatic mutation profiling of HACC was analysed using whole exome sequencing (WES). Multiplex fluorescence immunohistochemistry (mIHC) was used for tumor-infiltrating leukocytes and tertiary lymphoid structures (TLSs), while PD-L1 protein was detected by IHC. Our results indicate that the detection rates of HER2 positivity by IHC and FISH were 7.3% and 3.2% respectively, and HER2 amplification is correlated with distant tumour metastasis. The somatic mutation profiling revealed no differences between HACC and HER2-negative CRC. However, TP 53 strongly correlated with poor prognosis in HACC. Furthermore, tumor-infiltrating T cells and TLSs in the tumor immune microenvironment, as well as PD-L1 expression, were higher in HACC than in HER2-negative controls. However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC.

Background and aimsAn increasing number of studies have confirmed that non-textbook outcomes (non-TO) are a risk factor for the long-term outcome of malignant tumors. It is particularly important to identify the predictive factors of non-TO to improve the quality of surgical treatment. We attempted to construct two nomograms for preoperative and postoperative prediction of non-TO after laparoscopic hepatectomy for hepatocellular carcinoma (HCC).MethodsPatients who underwent curative-intent hepatectomy for HCC between 2014 and 2021 at two Chinese hospitals were analyzed. Using univariate and multivariate analyses, the independent predictors of non-TO were identified. The prediction accuracy is accurately measured by the receiver operating characteristic (ROC) curve and calibration curve. ROC curves for the preoperative and postoperative models, Child–Pugh grade, BCLC staging, and 8th TNM staging were compared relative to predictive accuracy for non-TO.ResultsAmong 515 patients, 286 patients (55.5%) did not achieve TO in the entire cohort. Seven and eight independent risk factors were included in the preoperative and postoperative predictive models by multivariate logistic regression analysis, respectively. The areas under the ROC curves for the postoperative and preoperative models, Child–Pugh grade, BCLC staging, and 8th TNM staging in predicting non-TO were 0.762, 0.698, 0.579, 0.569, and 0.567, respectively.ConclusionOur proposed preoperative and postoperative nomogram models were able to identify patients at high risk of non-TO following laparoscopic resection of HCC, which may guide clinicians to make individualized surgical decisions, improve postoperative survival, and plan adjuvant therapy against recurrence.

Phosphors with afterglow can be used as phosphor-convertors in AC-LEDs to reduce the scintillation because the phosphorescence compensates for decayed emission in milliseconds. To improve the phosphorescent intensity, Tm3+ was employed as a co-dopant in Sr2MgSi2O7: Eu2+ phosphors. Compared to the long afterglow induced by Dy3+ co-doping, a suitable concentration of Tm3+ increased the number of excited electrons of Eu2+ by an energy transfer process so that fluorescent intensity was improved. After switching off the excitation, the accumulated excited electrons accompanied by the de-trapped electrons from the oxygen vacancies led to an improved phosphorescence intensity of the Eu2+. The Sr2MgSi2O7: Eu2+, Tm3+ synthesized in this study is a promising candidate for phosphor-conversion in AC-LEDs. [ABSTRACT FROM AUTHOR]

Mass transport in frozen ground is typically regarded slow. However, a highly permeable path can exist in frozen saline sand if the unfrozen water is interconnected at the pore scale. We therefore should consider when the unfrozen water is connected and how permeable can frozen saline sand be, yet there are few studies. This research utilizes in‐situ X‐ray CT to evaluate unfrozen water connectivity and permeability in frozen saline sand considering effects of initial salt content, temperature, freezing rate, and temperature gradient. Results show that higher initial salt content and/or temperature, both of which results in a higher unfrozen water content, easily maintains unfrozen water connectivity. Rapid freezing minimizes the brine expulsion and permits a higher unfrozen water content hence better connectivity. Permeability in frozen saline sand can be several orders higher than the typically reported value, highlighting the potential presence of rapid mass transport through the connected unfrozen water. Plain Language Summary: Frozen aqueous sandy soils in nature often contain a lot of substances such as dissolved salts, gases, contaminants. Mass migration via unfrozen water is of vital importance to groundwater flow, greenhouse gas emission, even contaminated soil remediation. Permeability determination of unfrozen water is well‐studied in salt‐free soils. Our study shows there can be a highly conductive path in frozen saline sand when the unfrozen water is interconnected, even at a low unfrozen water saturation of 14%. The connectivity of unfrozen water remains at −20°C with an initial salt concentration similar to seawater. Rapid freezing causes better connectivity because less unfrozen water is squeezed out of the frozen sand during ice growth. Permeability in frozen saline sand can be several orders of magnitude higher than the typically reported value. These findings indicate that mass transport in frozen ground, via the connected unfrozen water, can be much more active than previously thought. Key Points: Pore‐scale unfrozen water can be interconnected, enabling fast mass transport below 0°C when soil contains saltRapid freezing enhances unfrozen water connectivity and permeability due to less and slower salt migration during freezingPermeability of frozen saline sand can be several orders of magnitude higher than that of salt‐free soil [ABSTRACT FROM AUTHOR]

On-chip optical modulators, which are capable of converting electrical signals into optical signals, constitute the foundational components of photonic devices. Photonics modulators exhibiting high modulation efficiency and low insertion loss are highly sought after in numerous critical applications, such as optical phase steering, optical coherent imaging, and optical computing. This paper introduces a novel accumulation-type vertical modulator structure based on a silicon photonics platform. By incorporating a high-K dielectric layer of ZrO2, we have observed an increase in modulation efficiency while maintaining relatively low levels of modulation loss. Through meticulous study and optimization, the simulation results of the final device structure demonstrate a modulation efficiency of 0.16 V·cm, with a mere efficiency–loss product of 8.24 dB·V.

Terrestrial water storage (TWS) is a pivotal component of the global water cycle, profoundly impacting water resource management, hazard monitoring, and agriculture production. The Gravity Recovery and Climate Experiment (GRACE) and its successor, the GRACE Follow-On (GFO), have furnished comprehensive monthly TWS data since April 2002. However, there are 35 months of missing data over the entire GRACE/GFO observational period. To address this gap, we developed an operational approach utilizing singular spectrum analysis and principal component analysis (SSA-PCA) to fill these missing data over mainland China. The algorithm was demonstrated with good performance in the Southwestern River Basin (SWB, correlation coefficient, CC: 0.71, RMSE: 6.27 cm), Yangtze River Basin (YTB, CC: 0.67, RMSE: 3.52 cm), and Songhua River Basin (SRB, CC: 0.66, RMSE: 7.63 cm). Leveraging two decades of continuous time-variable gravity data, we investigated the spatiotemporal variations in TWS across ten major Chinese basins. According to the results of GRACE/GFO, mainland China experienced an average annual TWS decline of 0.32 ± 0.06 cm, with the groundwater storage (GWS) decreasing by 0.54 ± 0.10 cm/yr. The most significant GWS depletion occurred in the Haihe River Basin (HRB) at −2.07 ± 0.10 cm/yr, significantly substantial (~1 cm/yr) depletions occurred in the Yellow River Basin (YRB), SRB, Huaihe River Basin (HHB), Liao-Luan River Basin (LRB), and Southwest River Basin (SWB), and moderate losses were recorded in the Northwest Basin (NWB, −0.34 ± 0.03 cm/yr) and Southeast River Basin (SEB, −0.24 ± 0.10 cm/yr). Furthermore, we identified that interannual TWS variations in ten basins of China were primarily driven by soil moisture water storage (SMS) anomalies, exhibiting consistently and relatively high correlations (CC > 0.60) and low root-mean-square errors (RMSE < 5 cm). Lastly, through the integration of GRACE/GFO and Global Land Data Assimilation System (GLDAS) data, we unraveled the contrasting water storage patterns between northern and southern China. Southern China experienced drought conditions, while northern China faced flooding during the 2020–2023 La Niña event, with the inverse pattern observed during the 2014–2016 El Niño event. This study fills in the missing data and quantifies water storage variations within mainland China, contributing to a deeper insight into climate change and its consequences on water resource management.

Organic amine and nanosilica were combined to create a nano-demulsifier, which was employed in the oil–water separation process of a condensate emulsion. The nano-demulsifier has the structure of hyperbranched polymers and the skeleton structure of hyperbranched nanomaterials, and displays the demulsification impact of organic amine polymers as well as the synergistic effect of nanomaterials. This nano-demulsifier has the potential to drastically reduce the quantity of condensate demulsifiers utilized in the gathering station. The dehydration rate of the condensate lotion in the gas gathering station can reach more than 95% only at a concentration of 1.0 wt.%. Its application can significantly increase the separation efficiency of the condensate emulsion as well as the quality of condensate oil. It has a positive impact on cost reduction and efficiency in gas well production. The mechanism of action of the demulsifier was also studied, and the results show that the demulsifier is a phase reverse demulsifier.

The electrostatic gravity gradiometer carried by the Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite is affected by accelerometer noise and other factors; hence, the observation data present complex error characteristics in the low-frequency domain. The accuracy of the recovered gravity field will be directly affected by the design of the filters based on the error characteristics of the gradient data. In this study, the applicability of various filters to different errors in observation is evaluated, such as the 1/f error and the orbital frequency errors. The experimental results show that the cascade filter (DARMA), which is formed of a differential filter and an autoregressive moving average filter (ARMA) filter, has the best accuracy for the characteristic of the 1/f low-frequency error. The strategy of introducing empirical parameters can reduce the orbital frequency errors, whereas the application of a notch filter will worsen the final solution. Frequent orbit changes and other changes in the observed environment have little impact on the new version gradient data (the data product is coded 0202), while the influence cannot be ignored on the results of the old version data (the data product is coded 0103). The influence can be effectively minimized by shortening the length of the arc. By analyzing the above experimental findings, it can be concluded that the inversion accuracy can be effectively improved by choosing the appropriate filter combination and filter estimation frequency when solving the gravity field model based on the gradient data of the GOCE satellite. This is of reference significance for the updating of the existing models.

Abstract The objective of this study was to predict the preoperative pathological grading and survival period of Pseudomyxoma peritonei (PMP) by establishing models, including a radiomics model with greater omental caking as the imaging observation index, a clinical model including clinical indexes, and a combined model of these two. A total of 88 PMP patients were selected. Clinical data of patients, including age, sex, preoperative serum tumor markers [CEA, CA125, and CA199], survival time, and preoperative computed tomography (CT) images were analyzed. Three models (clinical model, radiomics model and combined model) were used to predict PMP pathological grading. The models’ diagnostic efficiency was compared and analyzed by building the receiver operating characteristic (ROC) curve. Simultaneously, the impact of PMP’s different pathological grades was evaluated. The results showed that the radiomics model based on the CT’s greater omental caking, an area under the ROC curve ([AUC] = 0.878), and the combined model (AUC = 0.899) had diagnostic power for determining PMP pathological grading. The imaging radiomics model based on CT greater omental caking can be used to predict PMP pathological grading, which is important in the treatment selection method and prognosis assessment.

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the “eat me” signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the “don't eat me” signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

Introduction: Alport syndrome (AS; OMIM#308940) is a progressive hereditary kidney disease characterized by hearing loss and ocular abnormalities. According to the mode of inheritance, AS has three subtypes: X-linked (XL; OMIM#301050), autosomal recessive (AR; OMIM#203780), and autosomal dominant (AD; OMIM#104200). XLAS is caused by a pathogenic variant in COL4A5 (OMIM*303630) gene encoding type IV collagen (Col-IV) α5 chain, while ADAS and ARAS are consequences of a variant in COL4A3 (OMIM*120070) and COL4A4 (OMIM*120131) genes that encode Col-IV α3 and α4 chains, respectively. Usually, diagnosis of AS requires hereditary or pathological examinations. Splicing variants are hard to be determined as pathogenic or non-pathogenic based on the results of gene sequencing.Methods: This study focused on a splicing variant in COL4A5 gene, termed NM_000495.5: c.4298–20T>A, and to analyzed its authenticity and damaged α5 chain. In vitro minigene splicing assay was applied to investigate the effect of splicing variant, c.4298–20T>A, on COL4A5 mRNA synthesis. Molecular dynamics method was used to predict the capability of the responsible α5(IV) to form a triple helix.Results: The intron 46 of COL4A5 mRNA retained 18 bp, resulting in insertion of six amino acids behind the amino acid at position 1,433 of α5(IV). The predicted protein effect of this variant: p. (Pro1432_Gly1433insAspTyrPheValGluIle). As a consequence, the stability of α5(IV) secondary structure was impaired, probably leading to the unusual configuration of α345(IV).Discussion: Normally, splicing variant in COL4A5 gene can lead to phenotypes of XLAS, and the effect is associated with the extent of splicing. The patient reported here carried a c.4298–20T>A splicing variant in COL4A5 gene, and AS was highly suspected based on the pathology results. However, the patient did not manifest any ocular or ear abnormalities. We therefore present the c.4298–20T>A splicing variant in COL4A5 gene as likely-pathogenic splicing variant that leads to XLAS with mild phenotypes.

Tea is the most popular drink worldwide, and China is the largest producer of tea. Therefore, tea is an important commercial crop in China, playing a significant role in domestic and foreign markets. It is necessary to make accurate and timely maps of the distribution of tea plantation areas for plantation management and decision making. In the present study, we propose a novel mapping method to map tea plantation. The town of Menghai in the Xishuangbanna Dai Autonomous Prefecture, Yunnan Province, China, was chosen as the study area, andgg GF-1 remotely sensed data from 2014-2017 were chosen as the data source. Image texture, spectral and geometrical features were integrated, while feature space was built by SEparability and THresholds algorithms (SEaTH) with decorrelation. Object-Oriented Image Analysis (OOIA) with a Support Vector Machine (SVM) algorithm was utilized to map tea plantation areas. The overall accuracy and Kappa coefficient ofh the proposed method were 93.14% and 0.81, respectively, 3.61% and 0.05, 6.99% and 0.14, 6.44% and 0.16 better than the results of CART method, Maximum likelihood method and CNN based method. The tea plantation area increased by 4,095.36 acre from 2014 to 2017, while the fastest-growing period is 2015 to 2016.

The sustainability of the ecological environment has been greatly threatened. Based on carbon emissions and combined with the panel data of 30 provinces in China from 2003 to 2020, this paper studied the various mechanisms of industrial structure optimization and population agglomeration on carbon emissions. The fixed effect model, panel threshold model and spatial spillover model are used to study the direct and indirect effects of industrial structure optimization and population agglomeration on carbon emissions, and the robustness of the results is tested in various ways. In terms of direct effects, the industrial structure optimization has a significant negative effect on carbon emissions, and the significance level is 1%. Population agglomeration has a significant positive effect on carbon emissions, with a significance level of 1%. In terms of indirect effects, 1) by adding the cross term of industrial structure optimization and population agglomeration, it is proved that population agglomeration can promote the carbon emission reduction effect of industrial structure optimization. 2) Population agglomeration was used as the threshold variable to verify the interval effect of industrial structure optimization on carbon emission reduction. The results show that the industrial structure optimization has a double threshold effect of population agglomeration on carbon emissions, and the threshold values are 2.1137 and 5.9263, respectively. And the larger the population agglomeration interval, the weaker the inhibition effect of industrial structure optimization on carbon emissions. 3) The industrial structure optimization, population agglomeration and carbon emissions have significant spatial spillover effects. The industrial structure optimization in neighboring areas has a significant inhibitory effect on carbon emissions, and the population agglomeration in neighboring areas has a significant promoting effect on carbon emissions.

BackgroundPrevious studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates.MethodsPatients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions.ResultsMultivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction 65 years old. This result was confirmed by trend analysis (P for trend 65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.

The gravity anomaly and vertical gravity gradient due to anomalous geological bodies are mainly computed by numerical methods, so it is difficult and time-consuming to use the gravity-geological method to invert seafloor topography. This paper addresses this issue by deriving an expression for gravity generated by a cylinder based on a series expansion. The choice of number for terms in the series is estimated by comparing with the numerical method, especially when the depth H=4000m, the accuracy of 1mGal(1Gal=10-2m/s2) can be achieved when the series are 9. The expressions can be used to establish the relationships between the shape of an anomalous body and the generated vertical gravity and vertical gravity gradient, respectively. Finally, the potential applications of the expressions in inverting seafloor topography are illustrated by synthetic examples.

Abstract Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

Abstract Aberrant lipid metabolism is an essential feature of hepatocellular carcinoma (HCC). Fatty acid transport protein-5 (FATP5) is highly expressed in the liver and is involved in the fatty acid transport pathway. However, the potential role of FATP5 in the pathogenesis of HCC remains largely unknown. Herein, we showed that FATP5 was downregulated in HCC tissues and even much lower in vascular tumor thrombi. Low expression of FATP5 was correlated with multiple aggressive and invasive clinicopathological characteristics and contributed to tumor metastasis and a poor prognosis in HCC patients. FATP5 inhibited the epithelial–mesenchymal transition (EMT) process and suppressed HCC cell migration and invasion, while silencing FATP5 had the opposite effects. Mechanistically, knockdown of FATP5 promoted cellular glycolytic flux and ATP production, thus suppressing AMP-activated protein kinase (AMPK) and activating its downstream signaling mammalian target of rapamycin (mTOR) to support HCC progression and metastasis. Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells. Collectively, FATP5 served as a novel suppressor of HCC progression and metastasis partly by regulating the AMPK/mTOR pathway in HCC, and targeting the FATP5-AMPK axis may be a promising therapeutic strategy for personalized HCC treatment.

Abstract Background and aims Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. Methods From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. Results A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. Conclusions Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.