Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.

An Innovative Design to Enhance Osteoinductive Efficacy and Biomechanical Behavior of a Titanium Dental Implant.

The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine-premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.

A new TROP2-targeting antibody-drug conjugate shows potent antitumor efficacy in breast and lung cancers.

Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). AE and LDP can be separated and reassembled, and the reassembled LDM possesses cytotoxicity similar to that of native LDM; this has made LDM attractive in the preparation of gene-engineering drugs. We herein firstly prepared a new fusion protein hIMB1636-LDP composed of hIMB1636 and LDP by genetic engineering. This construct showed potent binding activities to recombinant antigen with a KD value of 4.57 nM, exhibited binding to Trop2-positive cancer cells and internalization and transport to lysosomes, and demonstrated powerful tumor-targeting ability in vivo. We then obtained the antibody-drug conjugate (ADC) hIMB1636-LDP-AE by molecular reconstitution. In vitro, hIMB1636-LDP-AE inhibited the proliferation, migration, and tumorsphere formation of tumor cells with half-maximal inhibitory concentration (IC50) values at the sub-nanomolar level. Mechanistically, hIMB1636-LDP-AE induced apoptosis and cell-cycle arrest. In vivo, hIMB1636-LDP-AE also inhibited the growth of breast and lung cancers in xenograft models. Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics.

Four sulfur-containing compounds with anti-colon cancer effect from marine-derived fungus Aspergillus terreus.

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

Bacillus coagulans TCI711 Supplementation Improved Nonalcoholic Fatty Liver by Modulating Gut Microbiota: A Randomized, Placebo-Controlled, Clinical Trial.

Background: Nonalcoholic fatty liver disease (NAFLD) has become one of the major problems of chronic liver disease worldwide. It not only causes damage to the liver but also engenders chronic hepatitis and cirrhosis. Recent studies have shown that regulating Bacillus coagulans can improve NAFLD. Objectives: This trial explores whether B. coagulans TCI711 (BCT) could ameliorate NAFLD. Methods: A total of 57 patients with NAFLD were recruited through FibroScan liver fibrosis scanner and divided into placebo (n = 28) and BCT-supplemented groups (n = 29). Specifically, 1 BCT probiotic capsule was supplemented daily for 8 wk. Furthermore, the blood, stool, and fatty liver content were then examined. Results: Parameters evaluated for liver and kidney indicators showed no side effects after supplementing BCT. A significant reduction of 8.7% in the fatty liver was achieved by effectively suppressing the grade of fatty liver as revealed by controlled attenuation parameter. BCT also regulated gut microbiota profiles, with significant increases observed in Bifidobacterium, Eubacterium, Ruminococcaceae, and Sellimonas compared with the baseline. Conclusions: BCT may improve NAFLD by regulating gut microbiota, and parameters evaluated for liver and kidney indicate no side effects.

Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.

Establishment of a forward primers-superposed amplification analysis for accurate aspirin pharmacogenomic measurement.

Genotyping of gDNA rs12041331 (PEAR1), rs6065 (GP1BA), and rs730012 (LTC4S) can provide systematic guidance on the use of aspirin. However, an accurate, reliable and economical approach to simultaneous detection of the above single nucleotide polymorphisms (SNPs) is not reported. Herein, we designed and substantiated an allele-specific (AS) forward primer-superposed amplification analysis for measurement of the SNPs in PEAR1, GP1BA and LTC4S genes, in which the values of ∆Cq (differences in threshold cycles between the wild-type forward primer-based assay and the mutated-type forward primer-based assay) were employed to decide genotype. Mismatch AS forward primers were screened with the singleplex amplification analysis. Moreover, Cq extension optimized by AS forward primer superposition was observed in the selected forward primer-based triplex analysis. Further, robustness assessment of the triplex analysis showed the amplification efficiency ranging from 0.9 to 1.1. Precision test demonstrated the coefficient of variation of less than 2%. And the detective results of 189 DNA samples was completely concordant with that of commercial Sanger sequencing. In summary, we developed a simple, accurate and economical approach to genotyping of rs12041331 (PEAR1), rs6065 (GP1BA) and rs730012 (LTC4S) to provide a valuable pharmacogenomics tool for guidance of aspirin delivery.

A meta-analysis of treatment for early-stage cervical cancer: open versus minimally invasive radical trachelectomy.

BACKGROUND: In previous systematic reviews, meta-analysis was lacking, resulting in the statistical difference between the data of different surgeries being impossible to judge. This meta-analysis aims to contrast the fertility results and cancer outcomes between open and minimally invasive surgery. METHOD: We systematically searched databases including PubMed, Embase, Cochrane, and Scopus to collect studies that included open and minimally invasive radical trachelectomy. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Eight studies (1369 patients) were incorporated into our study. For fertility results, the Open group excels MIS group in pregnancies-Third trimester delivery [OR = 2.68; 95% CI (1.29, 5.59); P = 0.008]. Nevertheless, there is no statistical difference in clinical pregnancy, miscarriage, and second-trimester rate. Concerning cancer outcomes, no difference was detected in the overall survival [OR = 1.56; 95% CI (0.70, 3.45); P = 0.27] and recurrence [OR = 0.63; 95% CI (0.35, 1.12); P = 0.12]. Concerning surgery-related outcomes, the comprehensive effects revealed that the estimated blood loss of the Open group was higher than that of the MIS group[MD = 139.40; 95% CI (79.05, 199.75); P < 0.0001]. However, there was no difference between the postoperative complication rate in the two groups [OR = 1.52; 95% CI (0.89, 2.60); P = 0.12]. CONCLUSION: This meta-analysis suggested that the fertility result of the Open group may be better than the MIS group, while the MIS group has better surgery-related outcomes. Owing to the poor cases of our study, a more robust conclusion requires more relevant articles in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022352999.

hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

Biomechanical stress distribution of medical inelastic fabrics with different porosity structures.

Clothing fit and pressure comfort play important role in clothing comfort, especially in medical body sculpting clothing (MBSC). In the present study, different body movements (forward bending, side bending, and twisting) were adopted to simulate and investigate the biomechanical stress distribution of the human body with three kinds of porosity inelastic MBSCs through the finite element analysis method. The elastic modulus of the investigated MBSCs was also measured by means of tensile testing. Analytical results showed that in the compression region during body movements, the investigated inelastic MBSCs endured less compression stress, and most of the stress was transmitted to the human body. Moreover, the stresses on the body surface were decreased with the porosity increasing. However, most of the von Mises stresses on the human body were in the desired pressure comfort range. Therefore, these results could provide potential information in the modification of MBSC for medical applications.

Elucidating the development, characterization, and antitumor potential of a novel humanized antibody against Trop2.

Trophoblast cell surface antigen 2 (Trop2) has emerged as a potential target for effective cancer therapy. In this study, we report a novel anti-Trop2 antibody IMB1636, developed using hybridoma technology. It exhibited high affinity and specificity (KD = 0.483 nM) in binding both antigens and cancer cells, as well as human tumor tissues. hIMB1636 could induce endocytosis, and enabled targeted delivery to the tumor site with an in vivo retention time of 264 h. The humanized antibody hIMB1636, acquired using CDR grafting, exhibited the potential to directly inhibit cancer cell proliferation and migration, and to induce ADCC effects. Moreover, hIMB1636 significantly inhibited the growth of MDA-MB-468 xenograft tumors in vivo. Mechanistically, hIMB1636 induced cell cycle arrest and apoptosis by regulating cyclin-related proteins and the caspase cascade. In comparison to commercialized sacituzumab, hIMB1636 recognized a conformational epitope instead of a linear one, bound to antigen and cancer cells with similar binding affinity, induced significantly more potent ADCC effects against cancer cells, and displayed superior antitumor activities both in vitro and in vivo. The data presented in this study highlights the potential of hIMB1636 as a carrier for the formulation of antibody-based conjugates, or as a promising candidate for anticancer therapy.

An Innovative Biofunctional Composite Hydrogel with Enhanced Printability, Rheological Properties, and Structural Integrity for Cell Scaffold Applications.

The present study was conducted to manipulate various biomaterials to find potential hydrogel formulations through three-dimensional (3D) bioprinting fabrication for tissue repair, reconstruction, or regeneration. The hydrogels were prepared using sodium alginate and gelatin combined with different concentrations of Pluronic F127 (6% (3 g), 8% (4 g), and 10% (5 g)) and were marked as AGF-6%, AGF-8%, and AGF-10%, respectively. The properties of the hydrogels were investigated using a contact angle goniometer, rheometer, and 3D bioprinter. In addition, the osteoblast-like cell line (MG-63) was used to evaluate the cell viability including hydrogels before and after 3D bioprinting. It was found that the ratio of contact angle was lowest at AGF-6%, and the rheological results were higher for all samples of AGF-6%, AGF-8%, and AGF-10% compared with the control sample. The printability indicated that the AGF-6% hydrogel possessed great potential in creating a cell scaffold with shape integrity. Moreover, the live/dead assay also presented the highest numbers of live cells before printing compared with after printing. However, the number of live cells on day 7 was higher than on day 1 before and after printing (** p < 0.01). Therefore, the combination of AGF-6% could be developed as a biofunctional hydrogel formulation for potential tissue regeneration applications.

Isolation and stereospecific synthesis of indole alkaloids with lipid-lowering effects from the marine-derived fungus Colletotrichum gloeosporioides BB4.

Seven undescribed compounds, colletotrichindoles A-E, colletotrichaniline A, and colletotrichdiol A, as well as three known compounds, (-)-isoalternatine A, (+)-alternatine A and 3-hydroxybutan-2-yl 2-phenylacetate were isolated from the marine-derived fungus Colletotrichu gloeosporioides BB4. The racemic mixtures colletotrichindole A，colletotrichindole C, and colletotrichdiol A were further separated by chiral chromatography to give three pairs of enantiomers (10S,11R,13S)/(10R,11S,13R)-colletotrichindole A, (10R,11R,13S)/(10S,11S,13R)-colletotrichindole C, and (9S,10S)/(9R,10R)-colletotrichdiol A, respectively. The chemical structures of seven undescribed compounds and the known compounds, (-)-isoalternatine A, and (+)-alternatine A were determined using a combination of NMR, MS, X-ray diffraction, ECD calculations, and/or chemical synthesis. All possible enantiomers of colletotrichindoles A-E were synthesized and used to determine the absolute configurations of the natural products by comparing their spectroscopic data and HPLC retention times on a chiral column. In addition, the X-ray crystal structures of the known compounds (-)-isoalternatine A and (+)-alternatine A were also obtained to confirm their absolute configurations. (10S,11R,13S)-Colletotrichindole A, colletotrichindole B, and (+)-alternatine A significantly reduced triglyceride levels in 3T3-L1 cells with EC50 values of 5.8, 9.0, and 1.3 µM, respectively.

Lentinuses A-B, two alkaloids from the marine-derived fungus Lentinus sajor-caju with potent anti-pulmonary fibrosis activity.

By adding natural amino acids into the medium as sole nitrogen source, twenty-four compounds, including two new alkaloids lentinuses A-B (1-2) with a rare oxazinone core in marine natural products, one new natural product 3-acetamido-4-phenylfurazan (3), 9ß-ergosterol (22) were firstly discovered from a marine fungus, and twenty known compounds (4-21, 23-24) were isolated from the marine-derived fungus Lentinus sajor-caju. The chemical structures of all these compounds were elucidated by HRMS, NMR spectroscopy and X-ray diffraction. Compounds 1-24 were evaluated for their inhibitory activity against TGF-ß1-induced collagen accumulation in human fetal lung fibroblasts (HFL1). Compounds 2, 3, 12, 22, and 23 showed potent activity against TGF-ß1-induced collagen accumulation and low toxicity to HFL1 cells. The binding mode of lentinus B (2) with TGF-ß1 receptor was then performed by using Schrödinger software, and the result showed that lentinus B possesses a strong binding force such as hydrogen bonding and hydrophobic interactions to the protein, which may provide a theoretical basis to design more potent anti-fibrotic drugs in the future.

18 F-FDG PET/CT of a Rare Sternal Osteoblastoma in a Man With History of Lymphoma.

ABSTRACT: A 27-year-old man, with a history of non-Hodgkin lymphoma 8 years ago, was admitted due to 9 months of persistent sternal pain. Chest CT revealed a mass in the sternum. 18 F-FDG PET/CT was performed, demonstrating a radioactive accumulation mass in the sternum, accompanied by massive osteogenesis and osteolysis. Histological and immunohistochemical analysis of ultrasound-guided fine-needle aspiration biopsy samples confirmed the diagnosis of aggressive osteoblastoma. We present a rare case of aggressive sternal osteoblastoma, instead of lymphoma recurrence, on 18 F-FDG PET/CT in an adult with history of lymphoma.

Strategy for Accurate Diagnosis by Contrast-Enhanced Ultrasound of Focal Liver Lesions in Patients Not at High Risk for Hepatocellular Carcinoma: A Preliminary Study.

OBJECTIVE: To develop an effective strategy for accurate diagnosis of focal liver lesions (FLLs) in patients with non-high risk for hepatocellular carcinoma (HCC). METHODS: From January 2012 to December 2015, consecutive patients with non-high risk for HCC who underwent contrast-enhanced ultrasound (CEUS) were included in this retrospective double-reader study. All patients were stratified into 2 different risks (intermediate, low-risk) groups according to criteria based on clinical characteristics, known as clinical risk stratification criteria. For the intermediate-risk group, the CEUS criteria for identifying benign lesions and HCCs were constructed based on selected CEUS features. The diagnostic performance of the clinical risk stratification criteria, and CEUS criteria for identifying benign lesions and HCCs was evaluated. RESULTS: This study included 348 FLLs in 348 patients. The sensitivity and specificity of the clinical risk stratification criteria for malignancy was 97.8 and 69.8%. Patients were classified as intermediate risk if they were male, or older than 40 years of age, or HBcAb positive, or having positive tumor markers. Otherwise, patients were classified as low risk. Among the 348 patients, 327 were in the intermediate-risk group and 21 were in the low-risk group. In the intermediate-risk group, the CEUS criteria for identifying benign lesions were any of the following features: 1) hyper/isoenhancement in the arterial phase without washout, 2) nonenhancement in all phases, 3) peripheral discontinuous globular enhancement in the arterial phase, 4) centrifugal enhancement or peripheral enhancement followed by no central enhancement, or 5) enhanced septa. The accuracy, sensitivity, and specificity of the CEUS criteria for identifying benign lesions were 94.5, 83.0, and 99.6%, respectively. Arterial phase hyperenhancement followed by mild and late washout (>60 seconds) was more common in HCC patients than in non-HCC patients (P < .001). Using arterial phase hyperenhancement followed by mild and late washout as the CEUS criteria for identifying HCCs, the sensitivity and specificity were 52.6 and 95.3%, but unfortunately, the positive predictive value was only 82.0%. For the low-risk group, no further analysis was performed due to the small sample size. CONCLUSIONS: Initial clinical risk stratification followed by assessment of certain CEUS features appears to be a promising strategy for the accurate diagnosis of FLLs in patients not at high risk for HCC.

Relationship Between Subclinical Cardiovascular Diseases and Cardiac Morpho-Functional Parameters in Preclinical Stage A/B Heart Failure Adults with Type 2 Diabetes.

Purpose: Type 2 diabetes mellitus (T2DM) is a common risk factor for cardiovascular disease which increases the risk of heart failure. This study aimed to determine whether clinical characteristics and subclinical cardiovascular disease (CVD) features are correlated with echocardiographic morpho-functional parameters of T2DM patients. Patients and Methods: Two hundred and fifty-five T2DM patients without a history of coronary heart disease were enrolled in this cross-sectional study. The demographic characteristics, glucose and lipid levels were assessed for each patient. Carotid ultrasonography and peripheral artery examination were performed to measure carotid intima-media thickness (cIMT), carotid plaque, ankle-brachial index (ABI), brachial artery pulse wave velocity (baPWV), and carotid-femoral pulse wave velocity (cfPWV). Furthermore, echocardiography was conducted to evaluate cardiac morphology and systolic and diastolic function. The relationship between clinical characteristics, subclinical cardiovascular diseases, and cardiac morpho-functional parameters was explored with the Pearson and stepwise multivariable linear regression analyses. Results: A total of 255 subjects aged 18-80 years were enrolled in the study. Multiple regression analysis revealed that left ventricular mass index (LVMI) was correlated with age (ß=0.463, p = 0.000) and systolic blood pressure (SBP) (ß=0.179, p = 0.003). Relative wall thickness (RWT) was related to cfPWV (ß=0.006, p = 0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (ß=0.000, p = 0.036). In contrast, left ventricular ejection fraction (LVEF) was inversely related to cIMT (ß=-0.925, p = 0.019). The ratio of the peak flow velocity of early diastole to atrial contraction (peak E/A) was correlated with age (ß=-0.014, p = 0.000), diastolic blood pressure (DBP) (ß=-0.006, p = 0.001) and cfPWV (ß=-0.025, p = 0.044). Conclusion: In preclinical stage A/B heart failure adults with T2DM, age, BP, HOMA-IR, cfPWV and cIMT are correlated with cardiac morpho-functional parameters.

Mechanism Underlying Metformin Action and Its Potential to Reduce Gastric Cancer Risk.

Diabetes mellitus is associated with a high risk of developing gastric cancer (GC). Metformin, which is conventionally used to treat type 2 diabetes, induces AMP-activated protein kinase signaling and suppresses gluconeogenesis. Recent studies have reported that metformin is associated with beneficial effects in cancer prevention and treatment owing to its anti-tumor effects. This makes metformin a potential medication for GC therapy. However, contradicting reports have emerged regarding the efficacy of metformin in reducing the risk of GC. This review summarizes the impact of metformin on mitigating GC risk by analyzing clinical databases. The mechanism underlying the anti-tumor effect of metformin on GC is also discussed.

Electrical Performance of 28 nm-Node Varying Channel-Width nMOSFETs under DPN Process Treatments.

The decoupled-plasma nitridation treatment process is an effective recipe for repairing the trap issues when depositing high-k gate dielectric. Because of this effect, electrical performance is not only increased with the relative dielectric constant, but there is also a reduction in gate leakage. In the past, the effect of nitridation treatment on channel-length was revealed, but a channel-width effect with that treatment was not found. Sensing the different nano-node channel-width n-channel MOSFETs, the electrical characteristics of these test devices with nitridation treatments were studied and the relationship among them was analyzed. Based on measurement of the VT, SS, Gm, ION, and IOFF values of the tested devices, the electrical performance of them related to process treatment is improved, including the roll-off effect of channel-width devices. On the whole, the lower thermal budget in nitridation treatment shows better electrical performance for the tested channel-width devices.

Calculation of high-order harmonic generation of atoms and molecules by combining time series prediction and neural networks.

High-order harmonic generation (HHG) from the interaction of ultra-intense laser pulses with atoms is an important tabletop short-wave coherent light source. Accurate quantum simulations of it present large computational difficulties due to multi-electron multidimensional effects. In this paper, the time-dependent response of hydrogen atoms is calculated using a time-series prediction scheme, the HHG spectrum is reconstructed very accurately. The accuracy of the forecasting is further improved by using a neural network scheme. This scheme is also applied to the simulation of the harmonic emission on multi-electron systems, and the applicability of the scheme is confirmed by the harmonic calculation of complex systems. This method is expected to simulate the nonlinear dynamic process of multi-electron atoms and molecules irradiated by intense laser pulses quickly and accurately.