[Understanding and enlightenment of theoretical construction of Huatuo Jiaji (EX-B 2)].

The theory of Huatuo Jiaji (EX-B 2) is the representative of the knowledge construction of ancient anatomy, reflecting the academic thought of Huatuo's school. Through deeply analyzing the classic theory of acupuncture and its cultural and historical materials, it is believed that the five-body constituents are the structural basis of Huatuo Jiaji (EX-B 2), qi and blood are the material one, while biaoben (the sites where meridian qi gathers and diffuses) and qijie (the common pathways through which meridian qi gathers) indicate its functions. Huatuo Jiaji (EX-B 2) reveals the rules of the transverse distribution of meridian points and the relevant indications, providing the theoretic foundation for acupuncture treatment. It highlights the importance of the anatomical knowledge in acupuncture effect and proposes a new idea for establishing an effective classification system of meridian points.

Self-Responsive Fluorescence Aptasensor for Lactoferrin Determination in Dairy Products.

In this study, a self-responsive fluorescence aptasensor was established for the determination of lactoferrin (Lf) in dairy products. Herein, the aptamer itself functions as both a recognition element that specifically binds to Lf and a fluorescent signal reporter in conjunction with fluorescent moiety. In the presence of Lf, the aptamer preferentially binds to Lf due to its specific and high-affinity recognition by folding into a self-assembled and three-dimensional spatial structure. Meanwhile, its reduced spatial distance in the aptamer-Lf complex induces a FRET phenomenon based on the quenching of 6-FAM by amino acids in the Lf protein, resulting in a turn-off of the fluorescence of the system. As a result, the Lf concentration can be determined straightforwardly corresponding to the change in the self-responsive fluorescence signal. Under the optimized conditions, good linearities (R2 > 0.99) were achieved in an Lf concentration range of 2~10 µg/mL for both standard solutions and the spiked matrix, as well as with the desirable detection limits of 0.68 µg/mL and 0.46 µg/mL, respectively. Moreover, the fluorescence aptasensor exhibited reliable recoveries (89.5-104.3%) in terms of detecting Lf in three commercial samples, which is comparable to the accuracy of the HPCE method. The fluorescence aptasensor offers a user-friendly, cost-efficient, and promising sensor platform for point-of-need detection.

Real-time precision detection algorithm for jellyfish stings in neural computing, featuring adaptive deep learning enhanced by an advanced YOLOv4 framework.

Introduction: Sea jellyfish stings pose a threat to human health, and traditional detection methods face challenges in terms of accuracy and real-time capabilities. Methods: To address this, we propose a novel algorithm that integrates YOLOv4 object detection, an attention mechanism, and PID control. We enhance YOLOv4 to improve the accuracy and real-time performance of detection. Additionally, we introduce an attention mechanism to automatically focus on critical areas of sea jellyfish stings, enhancing detection precision. Ultimately, utilizing the PID control algorithm, we achieve adaptive adjustments in the robot's movements and posture based on the detection results. Extensive experimental evaluations using a real sea jellyfish sting image dataset demonstrate significant improvements in accuracy and real-time performance using our proposed algorithm. Compared to traditional methods, our algorithm more accurately detects sea jellyfish stings and dynamically adjusts the robot's actions in real-time, maximizing protection for human health. Results and discussion: The significance of this research lies in providing an efficient and accurate sea jellyfish sting detection algorithm for intelligent robot systems. The algorithm exhibits notable improvements in real-time capabilities and precision, aiding robot systems in better identifying and addressing sea jellyfish stings, thereby safeguarding human health. Moreover, the algorithm possesses a certain level of generality and can be applied to other applications in target detection and adaptive control, offering broad prospects for diverse applications.

Mendelian randomization analysis reveals causal relationships between circulating cell traits and renal disorders.

Purpose: The aim of this study was to investigate the causal relationships between circulating cell traits and risk of renal disorders. Methods: We applied a comprehensive two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) from publicly available genome-wide association studies (GWAS) databases were utilized. Genetically predicted instrumental variables of human blood cell traits were extracted from Blood Cell Consortium (BCX) while data on renal diseases was obtained from Finngen consortium. The primary MR analysis was conducted using the inverse variance weighted (IVW) method, with the weighted median (WM) and MR-Egger models used as additional methods. Sensitivity analyses, including MR-PRESSO, radial regression and MR-Egger intercept were conducted to detect outliers and assess horizontal pleiotropy. We further utilized the leave-one-out analysis to assess the robustness of the results. Causal associations were considered significant based on false rate correction (FDR), specifically when the IVW method provided a pFDR < 0.05. Results: Our results demonstrated that both white blood cell (WBC) count (OR = 1.50, 95% CI = 1.10-2.06, pFDR = 0.033, pIVW = 0.011) and lymphocyte count (OR = 1.50, 95% CI = 1.13-1.98, pFDR = 0.027, pIVW = 0.005) were causally associated with a higher risk of IgA nephropathy. Furthermore, WBC count was identified as a significant genetic risk factor for renal malignant neoplasms (OR = 1.23, 95% CI = 1.06-1.43, pFDR = 0.041, pIVW = 0.007). Additionally, an increased level of genetically predicted eosinophils was found to be causally associated with a higher risk of diabetic nephropathy (OR = 1.21, 95% CI = 1.08-1.36, pFDR = 0.007, pIVW = 0.001). No evidence of pleiotropy was determined. Conclusion: Our findings provide evidence of causal associations of circulating WBC count, lymphocyte count and IgA nephropathy, WBC count and renal malignant neoplasms, and eosinophil count and diabetic nephropathy. These results have the potential to contribute to the development of novel diagnostic options and therapeutic strategies for renal disorders.

Transient spray combustion characteristics in a gas-liquid pintle rocket engine under acoustic excitation.

In order to investigate the acoustic oscillation characteristics of gas-liquid pintle rocket engines and elucidate the path by which spray combustion process provides energy to the combustor pressure oscillation, a LOX/GCH4 pintle engine with rectangular combustor was designed. By adding transverse velocity disturbance for the first time, the acoustic response of spray combustion process was simulated, and the effect of excitation amplitude on acoustic response was researched. Numerical results show that the adopted transverse velocity disturbance can excite the first-order transverse acoustic oscillation with same excitation frequency in the engine combustor. The acoustic response maintenance mechanism under extrinsic excitation is summarized for pintle engines. Besides, the temperature distribution inside the engine combustor tends to be uniform, and the low-frequency oscillation caused by the flame transverse swing gradually disappears. The amplitude of combustor pressure oscillation is dominated by excitement amplitude and phase difference between the pressure and heat release in combustion reaction region. In addition, the time-averaged combustor pressure can be amplified mainly by transverse velocity disturbance. The research work can provide a reference for related fire tests on the acoustic response of a subscale gas-liquid pintle engine.

Van der Waals Encapsulation by Ultra-thin Oxide for Air-Sensitive 2D Materials.

The ambient stability is one of the focal points for applications of 2D materials, especially for those well-known air-sensitive ones such as black phosphorus (BP) and transitional metal telluride. Traditional methods of encapsulation, such as atomic layer deposition of oxides and heterogeneous integration of hexagonal boron nitride, can hardly avoid removal of encapsulation layer when the 2D materials are encapsulated for further device fabrication, which causes complexity and damage during the procedure. Here, a van der Waals encapsulation method that allows direct device fabrication without removal of encapsulation layer is introduced using Ga2O3 from liquid gallium. Taking advantage of the robust isolation ability against ambient environment of the dense native oxide of gallium, hundreds of times longer retention time of (opto)electronic properties of encapsulated BP and MoTe2 devices is realized than unencapsulated devices. Due to the ultra-thin high-κ properties of Ga2O3, top-gated devices are directly fabricated with the encapsulation layer, simultaneously as a dielectric layer. This direct device fabrication is realized by selective etching of Ga2O3, leaving the encapsulated materials intact. Encapsulated 1T' MoTe2 exhibits high conductivity even after 150 days in ambient environment. This method is therefore highlighted as a promising and distinctive one compared with traditional passivation approaches. This article is protected by copyright. All rights reserved.

Vapor Deposition of Bilayer 3R MoS2 with Room-Temperature Ferroelectricity.

Two-dimensional ultrathin ferroelectrics have attracted much interest due to their potential application in high-density integration of non-volatile memory devices. Recently, 2D van der Waals ferroelectric based on interlayer translation has been reported in twisted bilayer h-BN and transition metal dichalcogenides (TMDs). However, sliding ferroelectricity is not well studied in non-twisted homo-bilayer TMD grown directly by chemical vapor deposition (CVD). In this paper, for the first time, experimental observation of a room-temperature out-of-plane ferroelectric switch in semiconducting bilayer 3R MoS2 synthesized by reverse-flow CVD is reported. Piezoelectric force microscopy (PFM) hysteretic loops and first principle calculations demonstrate that the ferroelectric nature and polarization switching processes are based on interlayer sliding. The vertical Au/3R MoS2/Pt device exhibits a switchable diode effect. Polarization modulated Schottky barrier height and polarization coupling of interfacial deep states trapping/detrapping may serve in coordination to determine switchable diode effect. The room-temperature ferroelectricity of CVD-grown MoS2 will proceed with the potential wafer-scale integration of 2D TMDs in the logic circuit.

COMMD10 inhibited DNA damage to promote the progression of gastric cancer.

PURPOSE: The copper metabolism MURR1 domain 10 (COMMD10) plays a role in a variety of tumors. Here, we investigated its role in gastric cancer (GC). METHODS: Online prediction tools, quantitative real-time PCR, western blotting and immunohistochemistry were used to evaluate the expression of COMMD10 in GC. The effect of COMMD10 knockdown was investigated in the GC cell lines and in in vivo xenograft tumor experiments. Western blotting and immunofluorescence were used to explore the relationships between COMMD10 and DNA damage. RESULTS: The expression of COMMD10 was upregulated in GC compared to that in para-cancerous tissue and correlated with a higher clinical TNM stage (P = 0.044) and tumor size (P = 0.0366). High COMMD10 expression predicted poor prognosis in GC. Knockdown of COMMD10 resulted in the suppression of cell proliferation, migration, and invasion, accompanied by cell cycle arrest and an elevation in apoptosis rate. Moreover, the protein expression of COMMD10 was decreased in cisplatin-induced DNA-damaged GC cells. Suppression of COMMD10 impeded DNA damage repair, intensified DNA damage, and activated ATM-p53 signaling pathway in GC. Conversely, restoration of COMMD10 levels suppressed DNA damage and activation of the ATM-p53 signaling cascade. Additionally, knockdown of COMMD10 significantly restrained the growth of GC xenograft tumors while inhibiting DNA repair, augmenting DNA damage, and activating the ATM-p53 signaling pathway in xenograft tumor tissue. CONCLUSION: COMMD10 is involved in DNA damage repair and maintains genomic stability in GC; knockdown of COMMD10 impedes the development of GC by exacerbating DNA damage, suggesting that COMMD10 may be new target for GC therapy.

The nuclear and mitochondrial genome assemblies of Tetragonisca angustula (Apidae: Meliponini), a tiny yet remarkable pollinator in the Neotropics.

BACKGROUND: The field of bee genomics has considerably advanced in recent years, however, the most diverse group of honey producers on the planet, the stingless bees, are still largely neglected. In fact, only eleven of the ~ 600 described stingless bee species have been sequenced, and only three using a long-read (LR) sequencing technology. Here, we sequenced the nuclear and mitochondrial genomes of the most common, widespread and broadly reared stingless bee in Brazil and other neotropical countries-Tetragonisca angustula (popularly known in Brazil as jataí). RESULTS: A total of 48.01 Gb of DNA data were generated, including 2.31 Gb of Pacific Bioscience HiFi reads and 45.70 Gb of Illumina short reads (SRs). Our preferred assembly comprised 683 contigs encompassing 284.49 Mb, 62.84 Mb of which (22.09%) corresponded to 445,793 repetitive elements. N50, L50 and complete BUSCOs reached 1.02 Mb, 91 contigs and 97.1%, respectively. We predicted that the genome of T. angustula comprises 17,459 protein-coding genes and 4,108 non-coding RNAs. The mitogenome consisted of 17,410 bp, and all 37 genes were found to be on the positive strand, an unusual feature among bees. A phylogenomic analysis of 26 hymenopteran species revealed that six odorant receptor orthogroups of T. angustula were found to be experiencing rapid evolution, four of them undergoing significant contractions. CONCLUSIONS: Here, we provided the first nuclear and mitochondrial genome assemblies for the ecologically and economically important T. angustula, the fourth stingless bee species to be sequenced with LR technology thus far. We demonstrated that even relatively small amounts of LR data in combination with sufficient SR data can yield high-quality genome assemblies for bees.

Significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues.

OBJECTIVE: The primary objective of this study is to explore the significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues. METHODS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methodologies were used to detect HER2 gene amplification, as well as the expression levels of HER2, p53, and Ki67 proteins, across a group of 78 gastric cancer cases. RESULTS: The expression rate of the HER2 protein was determined to be 43.6% (34/78), with 17.9% (14/78) categorized as HER2 protein 3 + , 14.1% (11/78) as HER2 protein 2 + , and 11.5% (9/78) as HER2 protein 1 + . Using FISH technology, the HER2 gene amplification rate was identified as 19.2% (15/78), including 3 cases of HER2 gene cluster amplification, 5 cases of large granular amplification, 4 cases of punctate amplification, and 3 cases of high polysomy. The positive rate of p53 in gastric cancer cells was 52.6% (41/78), with 62.8% (49/78) of patients exhibiting a ki67 proliferation index ≤ 30, and 37.2% (29/78) accounting for a ki67 proliferation index > 30. The expression rates of the HER2 gene, p53, and ki67 in gastric cancer tissues were significantly associated with both gastric cancer staging and lymph node metastasis (P < 0.05). CONCLUSION: The HER2 gene amplification rate and gene copy number exhibit a positive correlation with the expression rates of p53 and ki67. Combining these assessments can provide crucial insights into the assessment of metastatic potential, disease progression, and prognosis of gastric tumor cells. This holds paramount importance in steering the formulation of individualized treatment strategies.

Paternal obesity induces subfertility in male offspring by modulating the oxidative stress-related transcriptional network.

BACKGROUND/OBJECTIVE: The effects of fathers' high-fat diet (HFD) on the reproductive health of their male offspring (HFD- F1) remain to be elucidated. Parental obesity is known to have a negative effect on offspring fertility, but there are few relevant studies on the effects of HFD-F1 on reproductive function. METHODS: We first succeeded in establishing the HFD model, which provides a scientific basis in the analysis of HFD-F1 reproductive health. Next, we assessed biometric indices, intratesticular cellular status, seminiferous tubules and testicular transcriptomic homeostasis in HFD-F1. Finally, we examined epididymal (sperm-containing) apoptosis, as well as antioxidant properties, motility, plasma membrane oxidation, DNA damage, and sperm-egg binding in the epididymal sperm. RESULTS: Our initial results showed that HFD-F1 mice had characteristics similar to individuals with obesity, including higher body weight and altered organ size. Despite no major changes in the types of testicular cells, we found decreased activity of important genes and noticed the presence of abnormally shaped sperm at seminiferous tubule lumen. Further analysis of HFD-F1 testes suggests that these changes might be caused by increased vulnerability to oxidative stress. Finally, we measured several sperm parameters, these results presented HFD-F1 offspring exhibited a deficiency in antioxidant properties, resulting in damaged sperm mitochondrial membrane potential, insufficient ATP content, increased DNA fragmentation, heightened plasma membrane oxidation, apoptosis-prone and decreased capacity for sperm-oocyte binding during fertilization. CONCLUSION: HFD- F1 subfertility arises from the susceptibility of the transcriptional network to oxidative stress, resulting in reduced antioxidant properties, motility, sperm-egg binding, and elevated DNA damage. Schematic representation of the HFD-F1 oxidative stress susceptibility to subfertility. Notably, excessive accumulation of ROS surpasses the physiological threshold, thereby damaging PUFAs within the sperm plasma membrane. This oxidative assault affects crucial components such as mitochondria and DNA. Consequently, the sperm's antioxidant defense mechanisms become compromised, leading to a decline in vitality, motility, and fertility.

One-Pot Synthesis of Alkyl Functionalized Reduced Graphene Oxide Nanocomposites as the Lubrication Additive Enabling Enhanced Tribological Performance.

Recently, aiming for the enhanced dispersibility of graphene-based nanomaterials in lubricating oil matrices to serve as highly efficient lubricant additives, numerous modification approaches have been extensively studied. However, these previous modification routes usually involve a tedious multistep modification process or multitudinous toxic reagents, restricting their extensive practical application. In this work, novel graphene oxide (GO) nanoadditives (RGO-g-BO) featuring excellent durable dispersion capability and remarkable tribological performance were successfully prepared via an environmentally friendly one-step approach consisting of surface grafting of long-chain bromooctadecane (BO) and in situ chemical reduction. Benefiting from the greatly improved lipophilicity (resulting from the introduction of hydrophobic long-chain alkane groups and chemical reduction), along with the miniaturization effect, RGO-g-BO exhibits superior long-term dispersion stability in the finished oil. Moreover, the tribological properties results demonstrated that the finished oil filled with RGO-g-BO nanolubricants achieved an outstanding friction-reducing and antiwear performance. Particularly, under the optimum content of RGO-g-BO (as low as 0.005 wt%), the friction coefficient as well as the wear volume of the composite finished oil were greatly reduced by 13% and 53%, respectively, as compared with nascent finished oil. Therefore, in view of the advantages of low-cost, one-step facile synthesis, desirable dispersion capability, and remarkable tribological performance, RGO-g-BO holds great prospects as a highly efficient lubrication additive in the tribology field.

van der Waals Engineering of Charge Density Waves in One-Dimensional Nb6Te6 Nanowires.

One-dimensional (1D) systems have played a crucial role in the development of fundamental physics and practical applications. Recently, transition metal monochalcogenide (TMM) wires based on molybdenum (Mo) and tungsten (W) have emerged as promising platforms for investigating 1D physics in pure van der Waals (vdW) platforms. Here, we report on the bottom-up fabrication of Nb6Te6 wires down to the single-wire limit. The unique properties of Nb6Te6 single wire enable the realization of 1D charge density wave (CDW) phases in an isolated single TMM wire. Moreover, we revealed the appealing regulation of 1D CDW orders by van der Waals interactions at either the 1D-2D interface (i.e., rotation of a single wire along its wire axis) or the 1D-1D interface. Two rotation angles (30° and 0°) give rise to 3 × 1 and zigzag chain CDW morphologies, respectively, which exhibit pronounced differences in atomic displacement by a factor of 2. The interwire vdW coupling overwhelms its counterpart at the 1D-2D interface, thus locking the rotation angle (at 0°) as well as the interwire atomic registries. In contrast, interestingly, the phases of the charge oscillations are independent of the adjacent wires. The ability to tailor 1D charge orders provides a crucial addition to the toll set of vdW integrations beyond two-dimensional materials.

General Synthesis of Metal Indium Sulfide Atomic Layers for Photocatalysis.

The metal indium sulfides have attracted extensive research interest in photocatalysis due to regulable atomic configuration and excellent optoelectronic properties. However, the synthesis of metal indium sulfide atomic layers is still challenging since intrinsic non-van-der-Waals layered structures of some components. Here, a surfactant self-assembly growth mechanism is proposed to controllably synthesize metal indium sulfide atomic layers. Eleven types of atomic layers with tunable compositions, thickness, and defect concentrations are successfully achieved namely In2S3, MgIn2S4, CaIn2S4, MnIn2S4, FeIn2S4, ZnIn2S4, Zn2In2S5, Zn4In16S33, CuInS2, CuIn5S8, and CdIn2S4. The typical CaIn2S4 shows a defect-dependence activity for CO2 photoreduction. The designed S vacancies in CaIn2S4 can serve as catalytic centers to activate CO2 molecules via localized electrons for π-back-donation. The engineered S vacancies tune the non-covalent interaction with CO2 and intermediates, manages to tune the free energy, and lower the reaction energy barrier. As a result, the defect-rich CaIn2S4 displays 2.82× improved reduction rate than defect-poor CaIn2S4. Meantime, other components also display promising photocatalytic performance, such as Zn2In2S5 with a H2O2 photosynthesis rate of 292 µmol g-1 h-1 and CuInS2 with N2-NH4 + conversion rate of 54 µmol g-1 h-1. This work paves the way for the multidisciplinary exploration of metal indium sulfide atomic layers with unique photocatalysis properties.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

Exploring the regulatory role of FBXL19-AS1 in triple-negative breast cancer through the miR-378a-3p/OTUB2 axis.

The regulatory potential of long noncoding RNA (lncRNA) FBXL19-AS1 has been highlighted in various cancers, but its effect on triple-negative breast cancer (TNBC) remains unclear. Here, we aimed to elucidate the role of FBXL19-AS1 in TNBC and its underlying mechanism. RT-qPCR was employed to detect the expressions of FBXL19-AS1 and miR-378a-3p in tissues and cells. Immunohistochemical staining and western blot were utilized to detect the expression levels of proteins. Cell activities were detected using flow cytometry, CCK-8, and transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were deployed to investigate interactions of different molecules. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathways were used to analyze the downstream pathway. In vivo xenograft model was conducted to detect the effect of FBXL19-AS1 on tumor growth. FBXL19-AS1 was overexpressed in TNBC tissues and cell lines compared with counterparts. FBXL19-AS1 knockdown suppressed TNBC cell activities, whereas its overexpression exhibited the opposite effect. Mechanistically, FBXL19-AS1 was found to interact with miR-378a-3p. Further analysis revealed that miR-378a-3p exerted tumor-suppressive effects in TNBC cells. Additionally, miR-378a-3p targeted and downregulated the expression of ubiquitin aldehyde binding 2 (OTUB2), a deubiquitinase associated with TNBC progression. In vivo experiments substantiated the inhibitory effects of FBXL19-AS1 knockdown on TNBC tumorigenesis, and a miR-378a-3p inhibitor partially rescued these effects. The downstream pathway of the miR-378a-3p/OTUB2 axis was explored, revealing connections with proteins involved in modifying other proteins, removing ubiquitin molecules, and influencing signaling pathways, including the Hippo signaling pathway. Western blot analysis confirmed changes in YAP and TAZ expression levels, indicating a potential regulatory network. In summary, FBXL19-AS1 promotes exacerbation in TNBC by suppressing miR-378a-3p, leading to increased OTUB2 expression. The downstream mechanism may be related to the Hippo signaling pathway. These findings propose potential therapeutic targets for TNBC treatment.

New genetic insights into immunotherapy outcomes in gastric cancer via single-cell RNA sequencing and random forest model.

OBJECTIVE: The high mortality rate of gastric cancer, traditionally managed through surgery, underscores the urgent need for advanced therapeutic strategies. Despite advancements in treatment modalities, outcomes remain suboptimal, necessitating the identification of novel biomarkers to predict sensitivity to immunotherapy. This study focuses on utilizing single-cell sequencing for gene identification and developing a random forest model to predict immunotherapy sensitivity in gastric cancer patients. METHODS: Differentially expressed genes were identified using single-cell RNA sequencing (scRNA-seq) and gene set enrichment analysis (GESA). A random forest model was constructed based on these genes, and its effectiveness was validated through prognostic analysis. Further, analyses of immune cell infiltration, immune checkpoints, and the random forest model provided deeper insights. RESULTS: High METTL1 expression was found to correlate with improved survival rates in gastric cancer patients (P = 0.042), and the random forest model, based on METTL1 and associated prognostic genes, achieved a significant predictive performance (AUC = 0.863). It showed associations with various immune cell types and negative correlations with CTLA4 and PDCD1 immune checkpoints. Experiments in vitro and in vivo demonstrated that METTL1 enhances gastric cancer cell activity by suppressing T cell proliferation and upregulating CTLA4 and PDCD1. CONCLUSION: The random forest model, based on scRNA-seq, shows high predictive value for survival and immunotherapy sensitivity in gastric cancer patients. This study underscores the potential of METTL1 as a biomarker in enhancing the efficacy of gastric cancer immunotherapy.

Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Comprehensive prognostic and immunological analysis of Cullin2 in pan-cancer and its identification in hepatocellular carcinoma.

BACKGROUND: As a member of the Cullin family, Cullin2 (CUL2) is involved in the development and spread of different types of cancers. However, the precise role of CUL2 in human cancer remains largely elusive. METHODS: In this study, various databases were applied to observe the CUL2 expression. Kaplan-Meier and Spearman correlation analyses were employed to investigate the potential links between CUL2 level, patient prognosis, and the infiltration of immune cells. In addition, the association between CUL2 and the efficacy of immunotherapy in an immunotherapy cohort was investigated. Moreover, the expression and distribution of CUL2 in cells were observed using the Human Protein Atlas (THPA) database. Finally, clinical tissue specimens and in vitro function assays were conducted to validate the expressions and effects of CUL2 on the biological functions in hepatocellular carcinoma (HCC) cells. RESULTS: While there are variations in CUL2 expression across different organs and cell types, it is notably upregulated in a majority of tumor tissues. In addition, CUL2 gene mutations are common in multiple cancers with low mutation rates and CUL2 is closely related to the prognosis of some cancer's patients, some immune regulatory factors, TMB, MSI, MMR genes, and DNA methylation. Further, our results found that downregulating CUL2 inhibits the proliferation, and migration abilities. CONCLUSIONS: The expression of CUL2 has an impact on the prognosis of various tumors, and this correlation is particularly noteworthy due to its significant association with the infiltration of immune cells within tumors. CUL2 was an oncogene contributing to the progression of HCC.

Histopathological staging of atrophic lesions of gastric mucosa.

Objective: To study the histopathological staging of atrophic lesions of the gastric mucosa. Methods: Histology and immunohistochemistry were used to closely examine 2144 specimens of atrophic gastric mucosa that were taken from endoscopic biopsies. Results: When the gastric mucosa epithelium is affected by infection, chemical stimulation, immune factors, genetic factors, and other factors, it may cause an atrophy of gastric mucosa epithelium and a decrease in the number of glands, intestinal metaplasia, hyperplasia of smooth muscle fibers, and atrophy of stem cells in the proliferative zone. In this study, we characterized the above lesions as atrophic lesions of the gastric mucosa. Based on the morphological and histological characteristics of the lesion, as well as the law of cell proliferation and transformation during its occurrence and development, we propose five stages. We also noted the onset age, gender correlation, and histopathological characteristics of each stage of gastric mucosal atrophies. Conclusion: Understanding the pathological staging of gastric mucosal atrophy is essential for treating patients correctly and keeping track of changes in malignant cells. It is also very important in preventing the initiation of gastric cancer or from getting worse.