SIRT6 suppresses colon cancer growth by inducing apoptosis and autophagy through transcriptionally down-regulating Survivin.

SIRT6, an evolutionarily conserved histone deacetylase, has been identified as a novel direct downstream target of Akt/FoxO3a and a tumor suppressor in colon cancer in our previous research. Nevertheless, the precise mechanisms through which SIRT6 hinders tumor development remain unclear. To ascertain whether SIRT6 directly impacts Survivin transcription, a ChIP assay was conducted using an anti-SIRT6 antibody to isolate DNA. YM155 was synthesized to explore Survivin's role in mitochondrial apoptosis, autophagy and tumor progression. Our investigation into the regulation of Survivin involved real-time fluorescence imaging in living cells, real-time PCR, immunohistochemistry, flow cytometry, and xenograft mouse assays. In this current study, we delved into the role of SIRT6 in colon cancer and established that activated SIRT6 triggers mitochondrial apoptosis by reducing Survivin expression. Subsequent examinations revealed that SIRT6 directly binds to the Survivin promoter, impeding its transcription. Notably, direct inhibition of Survivin significantly impeded colon cancer proliferation by inducing mitochondrial apoptosis and autophagy both in vitro and in vivo. More interestingly, Survivin inhibition reactivated the Akt/FoxO3a pathway and elevated SIRT6 levels, establishing a positive feedback loop. Our results identify Survivin as a novel downstream transcriptional target of SIRT6 that fosters tumor growth and holds promise as a prospective target for colon cancer therapy.

Exploring the causal association between serum metabolites and erectile dysfunction: a bidirectional Mendelian randomisation study.

Erectile dysfunction is a common sexual disorder in men. Some studies have found a strong association between some serum metabolites and erectile dysfunction. To investigate this association further, we used bidirectional Mendelian randomisation to investigate causality and possible biological mechanisms.Firstly, this study screened the statistics of genome-wide association studies of serum metabolites and erectile dysfunction to obtain instrumental variables. Inverse variance weighting was used as the primary method for causal effect analysis of instrumental variables in forward or reverse Mendelian randomisation, and the results obtained by MR-Egger regression and the weighted median method were used as references. Subsequently, the metabolites causally associated with erectile dysfunction were subjected to replication analyses and meta-analyses, and the results of the meta-analyses were analysed by pathway analyses to find influential pathways. In this process, Mendelian randomisation results need to be assessed for stability and reliability using sensitivity analysis.It was found that a total of six serum metabolites were causally associated with erectile dysfunction in a forward Mendelian randomisation study. 1,3,7-trimethyluraten (0.85 (0.73-0.99), P = 0.0368), ergothioneine (0.65 (0.45-0.94), P = 0.0226) and gamma-glutamylglutamate (0.63 (0.46-0.88), P = 0.0059) were protective against the development of erectile dysfunction, whereas 2-hydroxyhippurate (1.10 (1.02-1.19), P = 0.0152), N2,N2-dimethylguanosine (1.57 (1.02-2.40), P = 0.0395) and octanoylcarnitine (1.38 (1.06-1.82), P = 0.0183) were able to induce the development of erectile dysfunction. In addition, metabolic pathway analysis showed that 1,3,7-trimethylurate was able to influence the development of erectile dysfunction via the caffeine metabolism pathway (P = 0.0454). On the other hand, reverse Mendelian randomisation analysis showed that erectile dysfunction reduced serum homocitrulline levels (0.99 (0.97-1.00), P = 0.0360). Sensitivity analyses, including heterogeneity tests and pleiotropy tests, confirmed the reliability of the results.In conclusion, this study demonstrated a bidirectional causal relationship between serum metabolites and erectile dysfunction using bidirectional Mendelian randomisation analysis and replication meta-analysis. On this basis, this study provides a new direction of thinking and strong evidence for the therapeutic application and adjunctive diagnosis of serum metabolites in erectile dysfunction, and provides a certain reference value for subsequent related studies.

The dynamics of N6-methyladenine RNA modification in resistant and susceptible rice varieties responding to rice stem borer damage.

N6-methyladenosine (m6A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m6A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m6A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m6A modifications against RSB. Upon RSB infestation, m6A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m6A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m6A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m6A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests.

Design of the sparrow search algorithm (SSA) for airborne radioactive hotspot detection.

In the context of using aircraft as a pivotal tool for detecting radioactive hotspots, the acquisition of radioactivity data was conducted through a CeBr3 scintillation crystal detector mounted on a helicopter. However, challenges arose, including managing extensive data volumes, computationally demanding tasks, and susceptibility to local optima issues. To address these challenges and leverage the benefits of the Sparrow Search Algorithm (SSA) in global optimization and convergence speed, an improved SSA was devised. This improved version integrated SSA principles with the intricacies of searching for radioactive hotspots. The algorithm employed a matrix segmentation method to process data matrices derived from measured data, aiming to enhance efficiency and accuracy. An empirical analysis was conducted, performing 100 iterations on an experimental matrix to scrutinize the impact of matrix segmentation. Computation times and results were compared across different segmentation levels, confirming the favorable algorithmic outcomes of the method. The practical viability and convergence stability of the algorithm were further assessed using genuine measured data, with segmented matrices generated for evaluation. Remarkably, a comparison between computational outcomes and manually identified data reaffirmed the algorithm's reliability in effectively detecting radioactive hotspots.

Two-stage extraction by partial grinding of impacted mandibular third molar in close proximity to the inferior alveolar nerve.

BACKGROUND: Extraction of impacted third molars often leads to severe complications caused by damage to the inferior alveolar nerve (IAN). AIM: To proposes a method for the partial grinding of an impacted mandibular third molar (IMM3) near the IAN to prevent IAN injury during IMM3 extraction. METHODS: Between January 1996 and March 2022, 25 patients with IMM3 roots near the IAN were enrolled. The first stage of the operation consisted of grinding a major part of the IMM3 crown with a high-speed turbine dental drill to achieve sufficient space between the mandibular second molar and IMM3. After 6 months, when the root tips were observed to be away from the IAN on X-ray examination, the remaining part of the IMM3 was completely removed. RESULTS: All IMM3s were extracted easily without symptoms of IAN injury after extraction. CONCLUSION: Partial IMM3 grinding may be a good alternative treatment option to avoid IAN injury in high-risk cases.

Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

Tyrosine hydroxylase plays crucial roles in larval cuticle formation and larval-pupal tanning in the rice stem borer, Chilo suppressalis.

The striped stem borer, Chilo suppressalis (Walker), a notorious pest infesting rice, has evolved a high level of resistance to many commonly used insecticides. In this study, we investigate whether tyrosine hydroxylase (TH), which is required for larval development and cuticle tanning in many insects, could be a potential target for the control of C. suppressalis. We identified and characterized the full-length cDNA (CsTH) of C. suppressalis. The complete open reading frame of CsTH (MW690914) was 1683 bp in length, encoding a protein of 560 amino acids. Within the first to the sixth larval instars, CsTH was high in the first day just after molting, and lower in the ensuing days. From the wandering stage to the adult stage, levels of CSTH began to rise and reached a peak at the pupal stage. These patterns suggested a role for the gene in larval development and larval-pupal cuticle tanning. When we injected dsCsTH or 3-iodotyrosine (3-IT) as a TH inhibitor or fed a larva diet supplemented with 3-IT, there were significant impairments in larval development and larval-pupal cuticle tanning. Adult emergence was severely impaired, and most adults died. These results suggest that CsTH might play a critical role in larval development as well as larval-pupal tanning and immunity in C. suppressalis, and this gene could form a potential novel target for pest control.

[Spatial-temporal Evolution and Quantitative Attribution of Habitat Quality in Typical Karst Counties of Guizhou Plateau].

The purpose of this study was to reveal the spatial and temporal evolution patterns of habitat quality in karst counties of Guizhou plateau and its driving factors and to provide scientific basis for balanced ecological conservation and sustainable development of karst regions. Using DEM data, meteorological data, socio-economic data, and four periods of land use data in 1989, 2003, 2010, and 2020, the InVEST model was used to analyze the spatial and temporal evolution characteristics of habitat quality in Puding County from 1989 to 2020 and to quantitatively detect the driving forces of its spatial divergence. The results were as follows:① Arable land and forest land were the main land use types in Puding County, which constituted the surface cover landscape matrix. Land use changes from 2003-2010 were the most significant, among which forest land had the largest increase of 86.42%; arable land was the most severely lost land use type, with an area decrease of 157.57 km2, mainly flowing to forest land and construction land. ② From 1989 to 2020, the average value of habitat quality index in Puding County increased from 0.60 to 0.73. Spatially, the distribution pattern of "high-low-high" was generally from northeast to southwest, with the high value areas of habitat quality mainly distributed in the woodland and grassland areas in the northeast and the low value areas concentrated in the construction land in the central and south areas. ③ Land use type was the primary factor affecting the spatial and temporal distribution of habitat quality, with an explanation of 91.00%. In the interaction detection, the interaction of any two influencing factors was greater than that of individual factors alone, and the interaction between land use type and average annual precipitation was the strongest, reaching 96.00%; the interaction with lithological factors reached 94.00%, with natural and human factors jointly dominating the spatial and temporal changes in habitat quality. From the results of this study, we concluded that the habitat quality of Puding County was generally good from 1989 to 2020, and the relationship between land use type changes and habitat quality was close. Optimizing the land use structure and reducing the influence of human activities are important to improve the habitat quality of Puding County.

Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

Defence and nutrition synergistically contribute to the distinct tolerance of rice subspecies to the stem borer, Chilo suppressalis.

Damage caused by the rice striped stem borer (SSB), Chilo suppressalis (Walker) (Lepidoptera: Pyralidae), is much more severe on indica/xian rice than on japonica/geng rice (Oryza sativa) which matches pest outbreak data in cropping regions of China. The mechanistic basis of this difference among rice subspecies remains unclear. Using transcriptomic, metabolomic and genetic analyses in combination with insect bioassay experiments, we showed that japonica and indica rice utilise different defence responses to repel SSB, and that SSB exploited plant nutrition deficiencies in different ways in the subspecies. The more resistant japonica rice induced patterns of accumulation of methyl jasmonate (MeJA-part of a defensive pathway) and vitamin B1 (VB1-a nutrition pathway) distinct from indica cultivars. Using gene-edited rice plants and SSB bioassays, we found that MeJA and VB1 jointly affected the performance of SSB by disrupting juvenile hormone levels. In addition, genetic variants of key biosynthesis genes in the MeJA and VB1 pathways (OsJMT and OsTH1, respectively) differed between japonica and indica rice and contributed to performance differences; in indica rice, SSB avoided the MeJA defence pathway and hijacked the VB1 nutrition-related pathway to promote development. The findings highlight important genetic and mechanistic differences between rice subspecies affecting SSB damage which could be exploited in plant breeding for resistance.

Causal effects of gut microbiota on the risk of erectile dysfunction: a Mendelian randomization study.

Erectile dysfunction ranks among the prevalent sexual disorders in men. Several studies have indicated a potential link between gut microbiota and erectile dysfunction. To validate this potential association, we were to screen statistical data from genome-wide association studies of gut microbiota and erectile dysfunction. p values of less than 1 × 10-5 were set as the threshold for screening instrumental variables that were strongly associated with gut microbiota. At the same time, in order to obtain more convincing findings, we further excluded instrumental variables with possible chain imbalance, instrumental variables with the presence of palindromes, instrumental variables with F-statistics less than 10, and instrumental variables associated with risk factors for erectile dysfunction. Five methods including inverse-variance weighted method, weighted median method, weighted mode, Mendelian randomization egger method and Mendelian randomization pleiotropy residual sum and outlier test were then used to analyse the 2591 instrumental variables obtained from the screening. We identified correlations between six gut microbiota and the risk of erectile dysfunction. The genus Ruminococcaceae UCG-013 exhibited an inverse association with the risk of developing erectile dysfunction (0.79 (0.65-0.97), P = 0.0214). Conversely, the genus Tyzzerella3 (1.13 (1.02-1.26), P = 0.0225), genus Erysipelotrichaceae UCG-003 (1.18 (1.01-1.38), P = 0.0412), genus LachnospiraceaeNC2004group (1.19 (1.03-1.37), P = 0.0191), genus Oscillibacter (1.23 (1.08-1.41), P = 0.0022), and family Lachnospiraceae (1.26 (1.05-1.52), P = 0.0123) demonstrated positive associations with an increased risk of erectile dysfunction. These sensitivity analyses of the gut microbiota were consistent. This study demonstrated a possible causal relationship between gut microbiota and erectile dysfunction risk through Mendelian randomization analysis, providing new potential possibilities for the prevention and treatment of erectile dysfunction.

Development of a compact helicon plasma source with two sets of ring array permanent magnets for the study of blue core plasma.

A compact helicon plasma source for the study of helicon plasma, especially for the study of blue core plasma, is designed and developed with permanent magnets (PMs). The structure of the PMs consists of two sets of ring array magnets with opposite magnetization. This structure can provide a higher magnetic field with fewer PMs, which is helpful for controlling the device's mass. A quartz tube with 50 cm in length, 5 cm in outer diameter, and 0.3 cm in thickness is used. Argon helicon plasma is produced at ∼38 sccm (3.4 Pa inlet chamber and 0.122 Pa diffusion chamber) by a radio frequency (RF) power of ∼13.56 MHz using a helical antenna under a high magnetic field (∼1600 G). Preliminary results measured by the Langmuir probe, photomultiplier tube (PMT), CCD, and Hall coil are applied to characterize the helicon plasma in this source, such as the mode transition and the formation of the blue core with the RF power variation. The device generates the blue core (W mode) plasma at a lower power of about 200 W, and the energy coupling efficiency is as high as 65%.

Evidence for Quantum Stripe Ordering in a Triangular Optical Lattice.

Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.

Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy.

BACKGROUND: Our previous study found that the telomerase-associated protein 1 (TEP1, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (RECQL5, rs820196) single nucleotide polymorphisms (SNPs) were associated with changes in heart rate (HR) ≥ 30% during peritoneal lavage with distilled water after gastrectomy. This study established a single tube method for detecting these three SNPs using two-dimensional (2D) polymerase chain reaction (PCR), and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability (HRV). AIM: To investigate whether genotypes, genetic patterns, SNP-SNP and SNP-environment interactions were associated with HRV. METHODS: 2D PCR was used to establish a single-tube method to detect TEP1 rs938886 and rs1713449 and RECQL5 rs820196, and the results were compared with those of sanger sequencing. After adjusting for confounders such as age, sex, smoking, hypertension, and thyroid dysfunction, a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns (codominant, dominant, overdominant, recessive, and additive) of the three SNPs and a risk ≥ 15% or ≥ 30% of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer. Gene-gene and gene-environment interactions were analyzed using generalized multifactor dimensionality reduction. RESULTS: The coincidence rate between the 2D PCR and sequencing was 100%. When the HRV cutoff value was 15%, the patients with the RECQL5 (rs820196) TC genotype had a higher risk of high HRV than those who had the TT genotype (odds ratio = 1.97; 95%CI: 1.05-3.70; P = 0.045). Under the codominant and overdominant models, the TC genotype of RECQL5 (rs820196) was associated with a higher risk of HR decrease relative to the TT and TT + CC genotypes (P = 0.031 and 0.016, respectively). When the HRV cutoff value was 30%, patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG-TT genotype carriers (P = 0.01). In the three-factor model of rs938886, rs820196, and rs1713449, patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers (P = 0.01). For rs820196, nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype (P = 0.04). When the HRV cutoff value was 15%, patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers (P = 0.04 and 0.01, respectively). Patients carrying the GC-CT-TC genotypes of rs938886, rs1713449, and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers (P = 0.02). When the HRV cutoff value was 15%, the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking (P = 0.022) and rs820196-hypertension (P = 0.043) models. Consistent with the results of the previous grouping, for rs820196, the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype (P = 0.01). CONCLUSION: The polymorphism of the RECQL5 and TEP1 genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.

Thermodynamic Evaluations of Amines as Hydrides or Two Hydrogen Ions Reductants and Imines as Protons or Two Hydrogen Ions Acceptors, as Well as Their Application in Hydrogenation Reactions.

Since the hydrogenation of imines (X) and the dehydrogenation of amines (XH2) generally involve the two hydrogen ions (H- + H+) transfer, the thermodynamic abilities of various amines releasing hydrides or two hydrogen ions as well as various imines accepting protons or two hydrogen ions are important and characteristic physical parameters. In this work, the pKa values of 84 protonated imines (XH+) in acetonitrile were predicted. Combining Gibbs free energy changes of amines releasing hydrides in acetonitrile from our previous work with the pKa(XH+) values, the Gibbs free energy changes of amines releasing two hydrogen ions and imines accepting two hydrogen ions were derived using Hess's law by constructing thermochemical cycles, and the thermodynamic evaluations of amines as hydrides or two hydrogen ions reductants and imines as protons or two hydrogen ions acceptors are well compared and discussed. Eventually, the practical application of thermodynamic data for amines and imines on hydrogenation feasibility, mechanism, and possible elementary steps was shown and discussed in this paper from the point of thermodynamics.

Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes.

BACKGROUND: Hepatocellular carcinoma (HCC) is difficult to diagnose with poor therapeutic effect, high recurrence rate and has a low survival rate. The survival of patients with HCC is closely related to the stage of diagnosis. At present, no specific serological indicator or method to predict HCC, early diagnosis of HCC remains a challenge, especially in China, where the situation is more severe. AIM: To identify risk factors associated with HCC and establish a risk prediction model based on clinical characteristics and liver-related indicators. METHODS: The clinical data of patients in the Affiliated Hospital of North Sichuan Medical College from 2016 to 2020 were collected, using a retrospective study method. The results of needle biopsy or surgical pathology were used as the grouping criteria for the experimental group and the control group in this study. Based on the time of admission, the cases were divided into training cohort (n = 1739) and validation cohort (n = 467). Using HCC as a dependent variable, the research indicators were incorporated into logistic univariate and multivariate analysis. An HCC risk prediction model, which was called NSMC-HCC model, was then established in training cohort and verified in validation cohort. RESULTS: Logistic univariate analysis showed that, gender, age, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II, gamma-glutamyl transferase, aspartate aminotransferase and hepatitis B surface antigen were risk factors for HCC, alanine aminotransferase, total bilirubin and total bile acid were protective factors for HCC. When the cut-off value of the NSMC-HCC model joint prediction was 0.22, the area under receiver operating characteristic curve (AUC) of NSMC-HCC model in HCC diagnosis was 0.960, with sensitivity 94.40% and specificity 95.35% in training cohort, and AUC was 0.966, with sensitivity 90.00% and specificity 94.20% in validation cohort. In early-stage HCC diagnosis, the AUC of NSMC-HCC model was 0.946, with sensitivity 85.93% and specificity 93.62% in training cohort, and AUC was 0.947, with sensitivity 89.10% and specificity 98.49% in validation cohort. CONCLUSION: The newly NSMC-HCC model was an effective risk prediction model in HCC and early-stage HCC diagnosis.

Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway.

Current therapy for acute myeloid leukemia (AML) is largely hindered by the development of drug resistance of commonly used chemotherapy drugs, including cytarabine, daunorubicin, and idarubicin. In this study, we investigated the molecular mechanisms underlying the chemotherapy drug resistance and potential strategy to improve the efficacy of these drugs against AML. By analyzing data from ex vivo drug-response and multi-omics profiling public data for AML, we identified autophagy activation as a potential target in chemotherapy-resistant patients. In THP-1 and MV-4-11 cell lines, knockdown of autophagy-regulated genes ATG5 or MAP1LC3B significantly enhanced AML cell sensitivity to the chemotherapy drugs cytarabine, daunorubicin, and idarubicin. In silico screening, we found that chloroquine phosphate mimicked autophagy inactivation. We showed that chloroquine phosphate dose-dependently down-regulated the autophagy pathway in MV-4-11 cells. Furthermore, chloroquine phosphate exerted a synergistic antitumor effect with the chemotherapy drugs in vitro and in vivo. These results highlight autophagy activation as a drug resistance mechanism and the combination therapy of chloroquine phosphate and chemotherapy drugs can enhance anti-AML efficacy.

Stacked SiGe nanosheets p-FET for Sub-3 nm logic applications.

The fabrication of vertically stacked SiGe nanosheet (NS) field-effect transistors (FETs) was demonstrated in this study. The key process technologies involved in this device fabrication are low pressure chemical vapor deposition SiGe/Si multilayer epitaxy, selective etching of Si layers over SiGe layers using tetramethyl-ammonium-hydroxide wet solution, and atomic layer deposition of Y2O3 gate dielectric. For the fabricated stacked SiGe NS p-GAAFETs with a gate length of 90 nm, ION/IOFF ratio of around 5.0 × 105 and subthreshold swing of 75 mV/dec were confirmed via electrical measurements. Moreover, owing to its high quality of Y2O3 gate dielectric, the device showed a very small drain-induced barrier-lowering phenomenon. These designs can improve the gate controllability of channel and device characteristics.

High-Performance P- and N-Type SiGe/Si Strained Super-Lattice FinFET and CMOS Inverter: Comparison of Si and SiGe FinFET.

This research presents the optimization and proposal of P- and N-type 3-stacked Si0.8Ge0.2/Si strained super-lattice FinFETs (SL FinFET) using Low-Pressure Chemical Vapor Deposition (LPCVD) epitaxy. Three device structures, Si FinFET, Si0.8Ge0.2 FinFET, and Si0.8Ge0.2/Si SL FinFET, were comprehensively compared with HfO2 = 4 nm/TiN = 80 nm. The strained effect was analyzed using Raman spectrum and X-ray diffraction reciprocal space mapping (RSM). The results show that Si0.8Ge0.2/Si SL FinFET exhibited the lowest average subthreshold slope (SSavg) of 88 mV/dec, the highest maximum transconductance (Gm, max) of 375.2 µS/µm, and the highest ON-OFF current ratio (ION/IOFF), approximately 106 at VOV = 0.5 V due to the strained effect. Furthermore, with the super-lattice FinFETs as complementary metal-oxide-semiconductor (CMOS) inverters, a maximum gain of 91 v/v was achieved by varying the supply voltage from 0.6 V to 1.2 V. The simulation of a Si0.8Ge0.2/Si super-lattice FinFET with the state of the art was also investigated. The proposed Si0.8Ge0.2/Si strained SL FinFET is fully compatible with the CMOS technology platform, showing promising flexibility for extending CMOS scaling.