Curcumin for gastric cancer: Mechanism prediction via network pharmacology, docking, and in vitro experiments.

BACKGROUND: Curcumin originates from the natural herb turmeric, and its antitumor effects have been known about for a long time. However, the mechanism by which curcumin affects gastric cancer (GC) has not been elucidated. AIM: To elucidate the potential mechanisms of curcumin in the treatment of GC. METHODS: Network pharmacological approaches were used to perform network analysis of Curcumin. We first analyzed Lipinski's Rule of Five for the use of Curcumin. Curcumin latent targets were predicted using the PharmMapper, SwissTargetPrediction and DrugBank network databases. GC disease targets were mined through the GeneCard, OMIM, DrugBank and TTD network databases. Then, GO enrichment, KEGG enrichment, protein-protein interaction (PPI), and overall survival analyses were performed. The results were further verified through molecular docking, differential expression analysis and cell experiments. RESULTS: We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets. The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways. Following PPI analysis, 6 hub targets were identified, namely, estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6 (CYP2B6). These factors are correlated with decreased survival rates among patients diagnosed with GC. Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes. The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation. mRNA levels of hub targets CYP3A4, MAPK14, CYP1A2, and CYP2B6 in BGC-823 cells were significantly increased in each dose group. CONCLUSION: Curcumin can play an anti-GC role through a variety of targets, pathways and biological processes.

Anisotropy-free arrayed waveguide gratings on X-cut thin film lithium niobate platform of in-plane anisotropy.

Arrayed waveguide grating is a versatile and scalable integrated light dispersion device, which has been widely adopted in various applications, including, optical communications and optical sensing. Recently, thin-film lithium niobate emerges as a promising photonic integration platform, due to its ability of shrinking largely the size of typical lithium niobate based optical devices. This would also enable multifunctional photonic integrated chips on a single lithium niobate substrate. However, due to the intrinsic anisotropy of the material, to build an arrayed waveguide grating on X-cut thin-film lithium niobate has never been successful. Here, a universal strategy to design anisotropy-free dispersive components on a uniaxial in-plane anisotropic photonic integration platform is introduced for the first time. This leads to the first implementation of arrayed waveguide gratings on X-cut thin-film lithium niobate with various configurations and high-performances. The best insertion loss of 2.4 dB and crosstalk of -24.1 dB is obtained for the fabricated arrayed waveguide grating devices. Applications of such arrayed waveguide gratings as a wavelength router and in a wavelength-division multiplexed optical transmission system are also demonstrated.

Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity.

OBJECTIVE: To evaluate if berberine can act on vitamin D receptors (VDR) and thereby regulate the expression of tight junction proteins (TJPs) in irritable bowel syndrame-diarrhea-predominant (IBS-D) rats. METHODS: The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation. After modeling, the model was evaluated and rats were divided into the control group and berberine treatment groups (0.85, 1.7 and 3.4 mg/kg, once a day for 2 weeks). The distal colon was obtained and colonic epithelial cells (CECs) were isolated and cultured after IBS-D model evaluation. The vitamin D receptor response element (VDRE) reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter. VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair, and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs. RESULTS: The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner (P<0.05). The activity of VDRE promoter was also effectively promoted by berberine (P<0.05). Berberine increased the expression of TJPs in IBS-D CECs (P<0.05). VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups (all P<0.05). RT-qPCR and Western blot results showed that compared with the blank group, expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups (all P<0.05). Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1 (P<0.05). CONCLUSION: Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity, and the main site of action is the N-terminal region of VDR.

Low-loss and broadband polarization-diversity edge coupler on a thin-film lithium niobate platform.

Fiber-to-chip coupling is an essential issue for taking high-performance integrated photonic devices into practical applications. On a thin-film lithium niobate platform, such a high-performance coupler featuring low loss, large bandwidth, and polarization independence is highly desired. However, the mode hybridization induced by the birefringence of lithium niobate seriously restricts a polarization-independent coupling. Here, we propose and experimentally demonstrate a high-performance and polarization-diversity cantilever edge coupler (EC) with the assistance of a two-stage polarization splitter and rotator (PSR). The fabricated cantilever EC shows a minimal coupling loss of 1.06 dB/facet, and the fully etched PSR structure shows a low insertion loss (IL) of -0.62 dB. The whole polarization-diversity cantilever EC exhibits a low IL of -2.17 dB and -1.68 dB for TE0 and TM0 mode, respectively, as well as a small cross talk of <-15 dB covering the wavelength band from 1.5 µm to 1.6 µm. A polarization-dependent loss <0.5 dB over the same wavelength band is also obtained. The proposed fiber-to-waveguide coupler, compatible with the fabrication process of popular thin-film lithium niobate photonic devices, can work as a coupling scheme for on-chip polarization-diversity applications.

Another Year of Record Heat for the Oceans.

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Crochet Hook Technique for Arthroscopic Anterior Talofibular Ligament Repair: Technique Note.

Ankle sprains can lead to chronic lateral ankle instability caused by an injured anterior talofibular ligament (ATFL), and surgery is often required when conservative treatments fail. BROSTROM surgery is considered the gold standard and has a definite curative effect. Advancements in arthroscopic surgery and improvements in implanted anchors have led to an increase in ATFL repairs using arthroscopic surgery. Arthroscopic AFTL repair is less invasive, and patients could experience faster recovery compared to open AFTL repair. To simplify the complicated suture-passing processes in arthroscopic AFTL repair, we developed a crochet hook and loop wire technique, which is described in this paper.

Compact 100GBaud driverless thin-film lithium niobate modulator on a silicon substrate.

Electro-optic (EO) modulators with a high modulation bandwidth are indispensable parts of an optical interconnect system. A key requirement for an energy-efficient EO modulator is the low drive voltage, which can be provided using a standard complementary metal oxide semiconductor circuity without an amplifying driver. Thin-film lithium niobate has emerged as a new promising platform, and shown its capable of achieving driverless and high-speed EO modulators. In this paper, we report a compact high-performance modulator based on the thin-film lithium niobate platform on a silicon substrate. The periodic capacitively loaded travelling-wave electrode is employed to achieve a large modulation bandwidth and a low drive voltage, which can support a driverless single-lane 100Gbaud operation. The folded modulation section design also helps to reduce the device length by almost two thirds. The fabricated device represents a large EO bandwidth of 45GHz with a half-wave voltage of 0.7V. The driverless transmission of a 100Gbaud 4-level pulse amplitude modulation signal is demonstrated with a power consumption of 4.49fj/bit and a bit-error rate below the KP4 forward-error correction threshold of 2.4×10-4.

Surface warming-induced global acceleration of upper ocean currents.

How the ocean circulation changes in a warming climate is an important but poorly understood problem. Using a global ocean model, we decompose the problem into distinct responses to changes in sea surface temperature, salinity, and wind. Our results show that the surface warming effect, a robust feature of anthropogenic climate change, dominates and accelerates the upper ocean currents in 77% of the global ocean. Specifically, the increased vertical stratification intensifies the upper subtropical gyres and equatorial currents by shoaling these systems, while the differential warming between the Southern Ocean upwelling zone and the region to the north accelerates surface zonal currents in the Southern Ocean. In comparison, the wind stress and surface salinity changes affect regional current systems. Our study points a way forward for investigating ocean circulation change and evaluating the uncertainty.

Stochastic Simulation of Typhoon in Northwest Pacific Basin Based on Machine Learning.

Typhoons have caused serious economic losses and casualties in coastal areas all over the world. The big size of the tropical cyclone sample by stochastic simulation can effectively evaluate the typhoon hazard risk, and the typhoon full-track model is the most popular model for typhoon stochastic simulation. Based on the advantages of machine learning in dealing with nonlinear problems, this study uses a backpropagation neural network (BPNN) to replace the regression model in the empirical track model, reestablishes the neural network model for track and intensity prediction in typhoon stochastic simulation, and constructs full-track typhoon events of 1000 years for Northwest Pacific basin. The validation results indicate that the BPNN can improve the accuracy of typhoon track and intensity prediction.

Another Record: Ocean Warming Continues through 2021 despite La Niña Conditions.

The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content (OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year's record value by 14 ± 11 ZJ (1 zetta J = 1021 J) using the IAP/CAS dataset and by 16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Niño-Southern Oscillation (ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans, and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.

Management of anticoagulants in delayed bleeding after endoscopic resection: A systematic review and meta-analysis.

Background and study aims Delayed bleeding and thrombotic events are uncontrolled adverse events that are hard to balance in patients receiving anticoagulants after endoscopic resection. The present study aims to assess the clinical effect of warfarin, when compared to direct oral anticoagulants (DOACs), in terms of delayed bleeding and thrombotic events. Methods A comprehensive electronic literature search was conducted for eligible literature. Pairwise meta-analyses were performed on outcomes of delayed bleeding and thrombotic events. Two networks within the Bayesian framework were established based on the management of anticoagulants and type of DOAC. Results Eight cohort studies with 2,046 patients were eligible for inclusion, including 1,176 patients treated with warfarin and 870 with DOACs. There was no significant difference between warfarin and DOACs, in terms of delayed bleeding (OR = 1.29, 95 % CI [0.99-1.69]) and thromboembolism (OR = 2.0, 95 % CI [0.32-12.39]). In the network meta-analyses for delayed bleeding, the rank probabilities revealed that the safest management was discontinuous warfarin without heparin bridge therapy (HBT). Rank probabilities for the types of DOACs demonstrated that the safest drug was dabigatran. Conclusions There was no significant difference in delayed bleeding and thromboembolism between warfarin and DOACs in patients receiving endoscopic treatment. In terms of delayed bleeding, discontinuous warfarin without HBT was suggested as the best management, and dabigatran was recommended as the best type of DOAC.

Propagation properties of autofocusing off-axis hollow vortex Gaussian beams in free space.

By solving the (2 + 1) dimensional Schrödinger equation in free space, we find that the autofocusing off-axis hollow vortex Gaussian beams (HVGBs) are analytically derived for the first time. The off-axis HVGBs can be adjusted by changing the off-axis coordinate (x0,y0) and topological charge n2. In particular, by increasing the off-axis coordinate (x0,y0), the self-focusing intensity can be increased. Besides, the self-focusing property can be more obvious. Furthermore, by increasing the hollow order n1, we can deepen the depth of focus, make the focus position further away, and increase the self-focusing intensity too. We also discuss other propagation properties that are used to enrich the autofocusing off-axis HVGBs, such as Poynting vector, angular momentum, gradient force, and maximum scattering force during propagation.

Elimination of Schistosoma japonicum Transmission in China: A Case of Schistosomiasis Control in the Severe Epidemic Area of Anhui Province.

Over the several decades, China has been incessantly optimizing control strategies in response to the varying epidemic situations of schistosomiasis. We evaluated continuously the changing prevalence under different control strategies of two villages, Sanlian and Guifan, in China through five phases lasting 37 years. We tested residents, calculated prevalence and discussed change causes. We found the prevalence in Sanlian did not differ significant from that of Guifan (p = 0.18) in 1981, but decreased to 2.66%, much lower than Guifan's 11.25%, in 1984 (p = 0). Besides, prevalence in Guifan increased to 21.25% in 1987, while in Sanlian it rose to 20.78% until 1989. Those data confirmed that praziquantel combined with snail control could better reduce the prevalence. From 1992 to 1994, the prevalence in the two villages displayed downtrends, which showed the World Bank Loan Project worked. From 1995 to 2004, repeated oscillations with no obvious change trend was seen. Since 2005, the prevalence in both villages has shown a significant downtrend (p < 0.05), which suggests the integrated strategy is effective. We considered the control strategies were implemented suitably in the study area under changing social circumstances. Adjusting the strategy in consideration of social transformations is necessary and vital. The experience may be useful for policy making of other epidemic areas with an analogous situation.

Effects of Yangzheng Sanjie Decoction-containing serum mediated by microRNA-7 on cell proliferation and apoptosis in gastric cancer.

Gastric cancer (GC) is one of the most common types of cancer and a leading cause of cancer-associated mortality. MicroRNAs (miRNAs/miRs) are demonstrated to function as oncomiRs or tumor-suppressor-miRs in GC. miR-7 has been identified to be a tumor suppressor of GC by targeting epidermal growth factor receptor (EGFR). In our previous study, Yangzheng Sanjie Decoction (YZSJD), a traditional Chinese formula, was identified to be effective in alleviating the symptoms and even postponing turnover of precancerous lesions. To elucidate the mechanism of YZSJD, the present study evaluated the effects of YZSJD of the GC MKN-45 cell line and investigated the underlying molecular mechanisms using YZSJD-containing serum (YCS). The expression of miR-7 in GC, normal and adjacent tissue samples was examined. The results demonstrated that YCS inhibited proliferation by inducing cell cycle arrest at the S phase, and significantly induced apoptosis compared with the control group. miR-7 was significantly downregulated in GC tissues compared with the matched ones. Using reverse transcription-quantitative polymerase chain reaction and western blot analysis, the expression of miR-7 was inversely associated with EGFR. This indicates that YCS inhibits proliferation and induces apoptosis of GC cells mediated by miR-7 targeting EGFR, which may be one of the mechanisms whereby YZSJD exerts its effects on GC.

Yangzheng Sanjie decoction regulates proliferation and apoptosis of gastric cancer cells by enhancing let-7a expression.

AIM: To explore the let-7a-mediated anti-cancer effect of Yangzheng Sanjie decoction (YZSJD) in gastric cancer (GC) cells. METHODS: YZSJD-containing serum (YCS) was prepared using traditional Chinese medicine serum pharmacology methods. After YCS treatment, cell proliferation and apoptosis were assessed by cell counting kit-8 assay and flow cytometry, respectively, and miRNA expression profiles were determined using qPCR arrays. Let-7a expression was examined by in situ hybridization in GC tissues and by qPCR in GC cells. c-Myc protein expression was detected by immunohistochemistry in GC tissues, and by Western blot in cell lines. RESULTS: YZSJD significantly inhibited proliferation and induced apoptosis in AGS and HS-746T GC cells. After treatment with YCS, the miRNA expression profiles were altered and the reduced let-7a levels in both cell lines were up-regulated, accompanied by a decrease in c-Myc expression. Moreover, decreased let-7a expression and increased c-Myc expression were observed during the progression of gastric mucosa cancerization. CONCLUSION: YZSJD inhibits proliferation and induces apoptosis of GC cells by restoring the aberrant expression of let-7a and c-Myc.

Assessment of the national schistosomiasis control program in a typical region along the Yangtze River, China.

Schistosomiasis remains a major public health problem in eastern China, particularly along the Yangtze River Basin. The latest national schistosomiasis control program (NSCP) was implemented in 2005 with the main goal of reducing the rate of infection to less than 5% by 2008 and 1% by 2015. To assess the progress, we applied a Bayesian spatio-temporal model to describe dynamics of schistosomiasis in Guichi, Anhui Province, China, using annual parasitological and environmental data collected within 41 sample villages for the period 2005-2011. Predictive maps of schistosomiasis showed that the disease prevalence remains constant and low. Results of uncertainty analysis, in the form of probability contour maps (PCMs), indicated that the first goal of "infection rate less than 5% by 2008" was fully achieved in the study area. More longitudinal data for schistosomiasis are needed for the assessment of the second goal of "infection rate less than 1% by 2015". Compared with the traditional way of mapping uncertainty (e.g., variance or mean-square error), our PCMs provide more realistic information for schistosomiasis control.

Multi-host model and threshold of intermediate host Oncomelania snail density for eliminating schistosomiasis transmission in China.

Schistosomiasis remains a serious public health issue in many tropical countries, with more than 700 million people at risk of infection. In China, a national integrated control strategy, aiming at blocking its transmission, has been carried out throughout endemic areas since 2005. A longitudinal study was conducted to determine the effects of different intervention measures on the transmission dynamics of S. japonicum in three study areas and the data were analyzed using a multi-host model. The multi-host model was also used to estimate the threshold of Oncomelania snail density for interrupting schistosomiasis transmission based on the longitudinal data as well as data from the national surveillance system for schistosomiasis. The data showed a continuous decline in the risk of human infection and the multi-host model fit the data well. The 25th, 50th and 75th percentiles, and the mean of estimated thresholds of Oncomelania snail density below which the schistosomiasis transmission cannot be sustained were 0.006, 0.009, 0.028 and 0.020 snails/0.11 m(2), respectively. The study results could help develop specific strategies of schistosomiasis control and elimination tailored to the local situation for each endemic area.

Role of microRNA-7 in digestive system malignancy.

There are several malignancies of the digestive system (including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA (miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.

Observed deep energetic eddies by seamount wake.

Despite numerous surface eddies are observed in the ocean, deep eddies (a type of eddies which have no footprints at the sea surface) are much less reported in the literature due to the scarcity of their observation. In this letter, from recently collected current and temperature data by mooring arrays, a deep energetic and baroclinic eddy is detected in the northwestern South China Sea (SCS) with its intensity, size, polarity and structure being characterized. It remarkably deepens isotherm at deep layers by the amplitude of ~120 m and induces a maximal velocity amplitude about 0.18 m/s, which is far larger than the median velocity (0.02 m/s). The deep eddy is generated in a wake when a steering flow in the upper layer passes a seamount, induced by a surface cyclonic eddy. More observations suggest that the deep eddy should not be an episode in the area. Deep eddies significantly increase the velocity intensity and enhance the mixing in the deep ocean, also have potential implication for deep-sea sediments transport.