Biodiversity conservation in the context of climate change: Facing challenges and management strategies.

Biodiversity conservation amidst the uncertainty of climate change presents unique challenges that necessitate precise management strategies. The study reported here was aimed at refining understanding of these challenges and to propose specific, actionable management strategies. Employing a quantitative literature analysis, we meticulously examined 1268 research articles from the Web of Science database between 2005 and 2023. Through Cite Spaces and VOS viewer software, we conducted a bibliometric analysis and thematic synthesis to pinpoint emerging trends, key themes, and the geographical distribution of research efforts. Our methodology involved identifying patterns within the data, such as frequency of keywords, co-authorship networks, and citation analysis, to discern the primary focus areas within the field. This approach allowed us to distinguish between research concentration areas, specifically highlighting a predominant interest in Environmental Sciences Ecology (67.59 %) and Biodiversity Conservation (22.63 %). The identification of adaptive management practices and ecosystem services maintenance are central themes in the research from 2005 to 2023. Moreover, challenges such as understanding phenological shifts, invasive species dynamics, and anthropogenic pressures critically impact biodiversity conservation efforts. Our findings underscore the urgent need for precise, data-driven decision-making processes in the face of these challenges. Addressing the gaps identified, our study proposes targeted solutions, including the establishment of germplasm banks for at-risk species, the development of advanced genomic and microclimate models, and scenario analysis to predict and mitigate future conservation challenges. These strategies are aimed at enhancing the resilience of biodiversity against the backdrop of climate change through integrated, evidence-based approaches. By leveraging the compiled and analyzed data, this study offers a foundational framework for future research and practical action in biodiversity conservation strategies, demonstrating a path forward through detailed analysis and specified solutions.

Prediction of Historical, Current, and Future Configuration of Tibetan Medicinal Herb Gymnadenia orchidis Based on the Optimized MaxEnt in the Qinghai-Tibet Plateau.

Climate change plays a pivotal role in shaping the shifting patterns of plant distribution, and gaining insights into how medicinal plants in the plateau region adapt to climate change will be instrumental in safeguarding the rich biodiversity of the highlands. Gymnosia orchidis Lindl. (G. orchidis) is a valuable Tibetan medicinal resource with significant medicinal, ecological, and economic value. However, the growth of G. orchidis is severely constrained by stringent natural conditions, leading to a drastic decline in its resources. Therefore, it is crucial to study the suitable habitat areas of G. orchidis to facilitate future artificial cultivation and maintain ecological balance. In this study, we investigated the suitable zones of G. orchidis based on 79 occurrence points in the Qinghai-Tibet Plateau (QTP) and 23 major environmental variables, including climate, topography, and soil type. We employed the Maximum Entropy model (MaxEnt) to simulate and predict the spatial distribution and configuration changes in G. orchidis during different time periods, including the last interglacial (LIG), the Last Glacial Maximum (LGM), the Mid-Holocene (MH), the present, and future scenarios (2041-2060 and 2061-2080) under three different climate scenarios (SSP126, SSP370, and SSP585). Our results indicated that annual precipitation (Bio12, 613-2466 mm) and mean temperature of the coldest quarter (Bio11, -5.8-8.5 °C) were the primary factors influencing the suitable habitat of G. orchidis, with a cumulative contribution of 78.5%. The precipitation and temperature during the driest season had the most significant overall impact. Under current climate conditions, the suitable areas of G. orchidis covered approximately 63.72 × 104/km2, encompassing Yunnan, Gansu, Sichuan, and parts of Xizang provinces, with the highest suitability observed in the Hengduan, Yunlin, and Himalayan mountain regions. In the past, the suitable area of G. orchidis experienced significant changes during the Mid-Holocene, including variations in the total area and centroid migration direction. In future scenarios, the suitable habitat of G. orchidis is projected to expand significantly under SSP370 (30.33-46.19%), followed by SSP585 (1.41-22.3%), while contraction is expected under SSP126. Moreover, the centroids of suitable areas exhibited multidirectional movement, with the most extensive displacement observed under SSP585 (100.38 km2). This study provides a theoretical foundation for the conservation of biodiversity and endangered medicinal plants in the QTP.

Polarization-stable single-mode 795†nm grating-coupled surface-emitting laser for quantum sensing.

We demonstrate a polarization-stable and single-mode grating-coupled surface-emitting laser (GCSEL) with high side-mode suppression ratio (SMSR) of ∼40 dB and orthogonal polarization suppression ratio (OPSR) of ∼25 dB around 795 nm. The fabricated devices have low threshold current of ∼4.8 mA and low electrical resistance of 53 Ω at 25 °C. Meanwhile, a low thermal resistance of ∼1 K/mW is achieved, which is comparable with that of the record of ever reported for vertical-cavity surface-emitting lasers (VCSELs). The far-field divergence angle of surface-emitting beam is ∼14.5°x14.7° at an injection current of 12 mA indicating a relatively good beam quality. Our results open what we believe is a new way to produce polarization-stable single-mode surface-emitting lasers with simple fabrication process. While the GCSEL is specifically designed for quantum sensing applications such as atomic clocks, magnetometers, and gyroscope, its performance in terms of low-power consumption, low thermal resistance, good beam qualities, and wafer-level testing are of particular interest for a wide range of applications.

Association between dietary vitamin C and abdominal aortic calcification among the US adults.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality, and vascular calcification has been highly correlated with CVD events. Abdominal aortic calcification (AAC) has been shown to predict subclinical CVD and incident CVD events. However, the relationship between vitamin C and abdominal aortic calcification remains unclear. OBJECTIVE: To investigate the relationship of dietary vitamin C with AAC among the adult population in the US. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2013-2014 provided the data for the cross-sectional study. 2297 subjects (1089 males) were included in the study. Two scoring systems, AAC 24-point scale (Kauppila) and AAC 8-point scale (Schousboe), were used for the measurement of AAC score. Dietary vitamin C intake was calculated as the average of two rounds of 24-h interview recall data and classified in tertiles for analysis. We applied weighted multiple regression analyses to assess the relationship of dietary vitamin C with AAC score and the risk of having AAC. To ensure the robustness of the findings, subgroup and sensitivity analyses were performed. Additionally, smooth curve fittings, using generalized additive models (GAM) were employed to visualize potential nonlinear relationships. Furthermore, an exploratory analysis on the relationship of vitamin C supplements with AAC was also conducted. RESULTS: The results showed that higher dietary vitamin C intake was related to a reduction in AAC score (AAC-24: ß = -0.338, 95% confidence interval [CI] -0.565, -0.111, P = 0.004; AAC-8: ß = -0.132, 95%CI -0.217, -0.047, P = 0.002), and lower risk of AAC (odds ratio [OR] = 0.807, 95%CI 0.659, 0.989, P = 0.038). However, the relationship of vitamin C supplements with AAC was not identified. CONCLUSIONS: The study revealed that higher intake of dietary vitamin C rather than vitamin C supplements was related to reduced AAC score and lower risk of AAC, indicating that diets rich in vitamin C are recommended due to its potential benefits for protecting against vascular calcification and CVD among the adult population in the US.

A nonsense mutation in VHL causing Von Hippel-Lindau syndrome in a large Chinese family-a genetic study of familial neoplastic disease.

Von Hippel-Lindau (VHL) syndrome is a multi-organ neoplastic disease characterized by highly vascular and cystic tumors in the central nervous system (CNS), retina, and visceral lesions, which are mainly caused by germline mutations in VHL. We aimed to detect novel mutations in VHL gene in families with VHL. Here, a large consanguineous four-generation family with variant phenotypes of VHL syndrome was recruited, and its molecular genetics were tested via Sanger sequencing. And various tools and databases were used to predict the variant pathogenicity, frequency, and protein function. Genetic investigation detected a c.351G > A nonsense mutation in VHL that altered the downstream reading frame and created a premature TGA stop signal, resulting in severely truncated pVHL (p.Trp117Ter). This mutation is absent from most public databases, and functional prediction bioinformatic tools demonstrated that this residue is conserved and that this variant is highly likely to be deleterious. The c.315G > A nonsense mutation in VHL is the causal mutation of this kindred that may lead to clear familial aggregation of VHL syndrome because of the dysfunction of the truncated pVHL.

Dietary supplementation with garcinol during late gestation alleviates disorders of bile acid metabolism and improves the performance of sows and newborn piglets.

The present study was conducted to evaluate the effects of dietary garcinol supplementation during late gestation on bile acid metabolism and performance of sows. Sixty sows (Duroc × Yorkshire × Landrace; second- or third-parity; n = 20) with disorder of bile acid metabolism were randomly divided into three groups: control diet (CON; basal diet), basal diet with 200 mg garcinol (Low Gar), and basal diet with 600 mg garcinol (High Gar) per kg of feed. The body weight (BW); backfat thickness and litter size of the sows; and birth weight, weaning weight, and mortality of piglets were recorded. Sows' blood was collected for the measurements of hematological parameters and antioxidative and immune indexes, and indicators related to bile acid metabolism, respectively. The colostrum and fecal samples of the sows were also collected for analysis of colostrum composition and apparent total tract nutrient digestibility. Garcinol had no effect on the BW and backfat thickness of the sows but significantly decreased the mortality and number of weak litter (P < 0.05). Moreover, the white blood cell counts, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in the plasma of the sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group, whereas the malondialdehyde (MDA) content was decreased (P < 0.05). Dietary supplementation with garcinol significantly reduced TBA concentrations (P < 0.05). The content of immunoglobulin A (IgA) and immunoglobulin G (IgG) in the plasma and in colostrum of sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group. In addition, dry matter (DM), Ash, and EE in the colostrum were similar between groups (P > 0.05), whereas the garcinol significantly increased the crude protein (CP) in the colostrum. The apparent total tract nutrient digestibility was similar between treatments. Garcinol treatment induced a gradually decreased (P > 0.05) the expression of genes involved in BA synthesis (CYP7A1, CYP8B1), BA uptake (NTCP, OATP1A2), BA secretion (BSEP and MRP2), BA detoxification (SULT2A1), and BA efflux into the blood circulation (OSTß). Collectively, this study indicates that sows fed with garcinol in late gestation showed relieved bile acid metabolism disorder and improved sows performance, antioxidative status, colostrum protein content, showing promise in natural plant extract nutrition for sows with disorder of bile acid metabolism.

The elevated maternal serum bile acid (BA) levels in late gestation leads to accumulation of BA in fetal tissues, and thus increases the risk of fetal mortality and metabolic disease of offspring. It has confirmed that BA disordered and oxidative damage are intimately related. Thus, studies about alleviating oxidative stress and facilitating BA metabolism in pregnant sows can be relevant. As an excellent antioxidative plant extract, garcinol has been widely used in dietary supplementation of rodents; however, the effect of dietary supplementation with garcinol on the bile acids disorders of sows in late gestation has rarely been reported. The present study provides the first evidence that dietary supplementation with garcinol during late gestation improved maternal BA metabolism of sows with disorder of BA metabolism, as well as the health and antioxidative status, colostrum protein content, showing promise in natural plant extract nutrition for sows with disorder of bile acid metabolism.

Triglyceride-glucose index and the risk of stroke in American adults: findings from the atherosclerosis risk in communities study.

OBJECTIVES: The associations between the triglyceride-glucose (TyG) index with subsequent stroke in American adults are unknown. The aim of this study was to determine the associations between baseline and trajectories of TyG index with subsequent stroke in American adults. METHODS: A total of 10,132 participants free of a history of stroke at baseline were included. We quantified the association of baseline and trajectories of TyG index with incident total stroke, ischemic stroke and intracerebral hemorrhage using Cox regression, restricted cubic splines and logistic regression analysis. RESULTS: There were 909 incident stroke cases over a median follow-up of 26.6 years. After adjustment for potential confounders, each unit increase in the TyG index was associated with a 32.1% higher risk of incident stroke. Compared with participants in the lowest quartile of the baseline TyG index, those in the highest quartile had a greater risk of incident stroke [HR (95% CI) 1.254 (1.014-1.552)]. Restricted cubic splines showed that the risk of stroke increased in participants with a higher TyG index, especially when the TyG index was > 8.6. Results were similar for incident ischemic stroke. Compared with participants in the lowest quartile of the baseline TyG index, those in the second quartile had a lower risk of intracerebral hemorrhage [HR (95% CI) 0.494 (0.262-0.931)]. Five discrete trajectories with stable TyG indexes at various levels at follow-up visits were identified, and parallel results were observed for the associations of trajectories of TyG index with outcomes. CONCLUSIONS: The TyG index independently predict stroke progression.

Effects of different processing techniques of palm kernel cake on processing quality of pellet feed, nutrient digestibility, and intestinal microbiota of pigs.

The present study was conducted to investigate the effects of extrusion, fermentation, and enzymolysis of palm kernel cake on processing quality of pellet feed, nutrient digestibility, and intestinal microbiota of pigs. First, the pretreatment parameters of extrusion, enzymolysis, and fermentation of palm kernel cake were optimized. Then, PKC after three processing techniques were used to prepare pellet feed. A total of 160 crossbred piglets (Duroc × Landrace × Yorkshire) with an average body weight of 28 ±â€…0.5 kg were used in an 8-wk feeding experiment. Pigs were randomly assigned to five treatments with four replicates per treatment and eight pigs per replicates. The five experimental groups were as follows: basal diet group (whole corn-soybean meal), 10% PKC group (PKC), 10% extrusion PKC group (PPKC), 10% enzymolysis PKC group (EPKC), and 10% fermented PKC group (FPKC), respectively. At the end of the experiment, four pigs from each treatment (randomly collected one pig per pen) were sacrificed by administering a pentobarbital overdose, the gut and blood samples were collected for the quantification analysis of microbiota, hematological parameters, and apparent total tract nutrient digestibility. The results showed that all three processing techniques significantly decreased the contents of crude fiber of PKC (P < 0.01), pulverization rate (P < 0.01), powder content (P < 0.01), and increased the hardness and gelatinization starch of pellet feed (P < 0.05) compared to PKC group. In addition, PPKC significantly improved the dry matter, crude protein, and ether extract content, blood indices and average daily feed intake compared to PKC group (P < 0.01), while the parameters were similar among FPKC, EPKC, and control group (P > 0.01). Furthermore, all three processing techniques significantly increased the Lactobacillus and decreased the Escherichia levels in feces or gut compared to PKC. Collectively, extrusion, fermentation, and enzymolysis of PKC had positively enhanced the pellet quality, growth performance, nutrient digestibility, and gut microbiota, extrusion exhibited a superior feeding effect compared to fermentation and enzymolysis.

Palm kernel cake (PKC) has lower nutritional value compared with soybean meal, cottonseed meal, and rapeseed meal, but its cost advantage is great, and it has been gradually used in the ruminant feeding. Due to its high crude fiber content, the processing technique applied to the PKC has a significant impact on its effectiveness. However, the different processing techniques of PKC on pellet quality, and performance of pigs have been poorly reported. The present study was conducted to investigate the effects of extrusion, fermentation, and enzymolysis pretreatment of PKC on processing quality of pellet feed, nutrient digestibility (in vivo), and intestinal microbiota of growing­finishing pigs. This study provides the optimal processing parameters of the three processing techniques, and demonstrated that PKC after processing could significantly improve the pellet quality, performance, and intestinal microbiota of growing­finishing pigs, while extrusion exhibited a superior feeding effect compared to fermentation and enzymolysis.

Efficacy and Safety of Oral Anticoagulants in Older Adult Patients With Atrial Fibrillation: Pairwise and Network Meta-Analyses.

OBJECTIVE: To evaluate the efficacy and safety of oral anticoagulants for older adult patients with atrial fibrillation (AF). DESIGN: Pairwise and network meta-analyses. SETTING AND PARTICIPANTS: Patients with AF aged ≥75 years. METHODS: PubMed, Embase, and the Cochrane library were searched for published randomized controlled trials and adjusted observational studies evaluating the use of a non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonist, or antiplatelet drug for the prevention of stroke. The primary efficacy and safety outcomes were the composite of stroke and systemic embolism (SSE) and major bleedings. RESULTS: This study included 38 studies enrolling 1,022,908 older adult patients with AF. Results from pairwise meta-analyses showed that NOACs were superior to warfarin for all outcomes, except that dabigatran increased the risk of gastrointestinal (GI) bleedings. Aspirin was associated with a higher risk of SSE and ischemic stroke than warfarin or NOACs. Results of network meta-analyses indicated that apixaban significantly reduced the risk of SSE, major bleedings, and GI bleedings than warfarin, rivaroxaban, and dabigatran. Apixaban, edoxaban, rivaroxaban, and dabigatran reduced the risk of ischemic stroke and intracranial bleeding compared to warfarin. Dabigatran showed lower risk of all-cause mortality than warfarin and of intracranial bleeding than rivaroxaban. CONCLUSIONS AND IMPLICATIONS: NOACs are of at least equal efficacy, or even superior to warfarin. The safety profile of individual NOAC agents was significantly different, as apixaban performs better than the other oral anticoagulants in reducing major bleeding and GI bleeding, whereas dabigatran increased the risk of GI bleeding.

The study of self-regulating α-TCP based composite by micro/nano scaled silk fibroin and α-CSH on physicochemical and biological properties of bone cement.

A novel self-hardening α-tricalcium phosphate (α-TCP) bone cement complexed with different content of α-calcium sulfate hemihydrate (α-CSH) and micrometer hydroxyapatite mineralized silk fibroin (HA-SF) using micro/SF as curing liquid has been investigated in this work, which was capable of tunable setting time, degradation, mechanical property and ability to anti-washout. After addition 0 ∼ 25% α-CSH to the α-TCP cement with SFFs as curing liquid, it shortened the setting time of the modified composite to 10 ∼ 30 min. Furthermore, the addition of SFFs improved the compressive strength of the composite from 5.41 MPa to 9.44 MPa. The composites with both Na2HPO4 and SFFs as curing liquid showed good anti-collapse performance. The weight loss ratio of bone cement was -0.18 ∼ 12.08% in 4 weeks when the content of α-CSH in α-TCP/α-CSH was between 0 ∼ 25 wt%. During the degradation of α-CSH, the amorphous α-TCP were deposited as hydroxyapatite to formed a plate-like products on the surface of composite. Compared to the composite with Na2HPO4 solution as the curing liquid, alkaline phosphatase (ALP) activity of the composites using SFFs as curing liquid were maintained at high levels on the 14th day especially when the Ca/P ratio was 1.7. This study provides a theoretical basis for the regeneration of bone defects guided by bone cement materials.

Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α.

The conversion of skeletal muscle fiber from fast-twitch to slow-twitch is crucial for sustained contractile and stretchable events, energy homeostasis, and anti-fatigue ability. The purpose of our study was to explore the mechanism and effects of garcinol on the regulation of skeletal muscle fiber type transformation. Forty 21-day-old male C57/BL6J mice (n = 10/diet) were fed a control diet or a control diet plus garcinol at 100 mg/kg (Low Gar), 300 mg/kg (Mid Gar), or 500 mg/kg (High Gar) for 12 weeks. The tibialis anterior (TA) and soleus muscles were collected for protein and immunoprecipitation analyses. Dietary garcinol significantly downregulated (p < 0.05) fast myosin heavy chain (MyHC) expression and upregulated (p < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased (p < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased (p < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased (p < 0.05) lactate dehydrogenase activity and increased (p < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased (p < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced (p < 0.05) the expression of fast MyHC but increased (p < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased (p < 0.05). Garcinol promotes the transformation of skeletal muscle fibers from the fast-glycolytic type to the slow-oxidative type through the p300/PGC-1α signaling pathway in C2C12 myotubes.

Dietary embelin supplementation during mid-to-late gestation improves performance and maternal-fetal glucose metabolism of pigs.

This study aimed to evaluate the effects of dietary embelin supplementation during late gestation (from days 60 to 110) on performance and maternal-fetal glucose metabolism of pigs. Sixty sows (Duroc × Yorkshire × Landrace; parity = 1.68 ±â€…0.03; N = 20) were randomly divided into three gestation (day 60 of pregnancy) treatments, Control pigs (CON) were fed a basal diet, and the other animals were fed a basal diet supplemented with 200 or 600 mg/kg embelin per kg of feed. The body weight, backfat thickness and litter size of the sows, and birth weight and mortality of piglets were recorded. Sows' blood and piglets' umbilical cord blood were collected for the measurements of hematological parameters and anti-oxidative and immune indexes, and maternal-fetal glucose metabolism parameters, respectively. The colostrum and milk and fecal samples of the sows were also collected for analysis of milk composition and apparent total tract nutrient digestibility. Dietary embelin had no effect on the BW and backfat thickness of the sows but significantly increased the birth weight of piglets (P < 0.05) and decreased the mortality (P < 0.05). Moreover, the white blood cell counts (day 90), neutrophil count and mean cell hemoglobin (day 110), total anti-oxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) content of the sows were increased significantly (P < 0.05) in the embelin groups than that in the CON group, whereas the malondialdehyde (MDA) content was decreased (P < 0.05). Embelin significantly increased immunoglobulin A (IgA) and immunoglobulin G (IgG) content in plasma of piglets as well as those in colostrum and milk of sows than the CON treatment (P < 0.05). In addition, dry matter, ash, and ether extract in the colostrum were similar between groups (P > 0.05), whereas the embelin significantly increased the crude protein in the milk. The apparent total tract nutrient digestibility was similar between treatments (P > 0.05). The embelin treatment significantly increased the glucose levels and lactate dehydrogenase B (LDHB) activity in sows plasma, and decreased the lactate levels in both sows and fetuses plasma (P < 0.05). Collectively, this study indicates that sows fed with embelin in mid-to-late gestation showed improved maternal health and anti-oxidative status, milk protein content, and maternal-fetal glucose metabolism, showing promise in natural plant extract nutrition for sows.

Abnormal glucose metabolism in sows in late gestation can lead to incapacity of sow production, and even reproductive disorders. It has been confirmed that inefficient glucose utilization and oxidative damage are intimately related. Thus, studies about alleviating oxidative stress and facilitating glucose metabolism in pregnant sows can be relevant. As an excellent anti-oxidative plant extract, embelin has been widely used in dietary supplementation of rodents, however, the effect of dietary supplementation with embelin on the performance of sows and newborn piglets, as well as on the glucose metabolism has rarely been reported. The present study provides the first evidence that dietary supplementation with embelin during mid-to-late gestation improved maternal immune and oxidative status, the milk quality as well as the glucose metabolism of both sows and piglets, suggesting that embelin may be a promising natural plant extractive of nutrition for sows especially during mid-to-late pregnancy and lactation.

Artificial intelligence reveals features associated with breast cancer neoadjuvant chemotherapy responses from multi-stain histopathologic images.

Advances in computational algorithms and tools have made the prediction of cancer patient outcomes using computational pathology feasible. However, predicting clinical outcomes from pre-treatment histopathologic images remains a challenging task, limited by the poor understanding of tumor immune micro-environments. In this study, an automatic, accurate, comprehensive, interpretable, and reproducible whole slide image (WSI) feature extraction pipeline known as, IMage-based Pathological REgistration and Segmentation Statistics (IMPRESS), is described. We used both H&E and multiplex IHC (PD-L1, CD8+, and CD163+) images, investigated whether artificial intelligence (AI)-based algorithms using automatic feature extraction methods can predict neoadjuvant chemotherapy (NAC) outcomes in HER2-positive (HER2+) and triple-negative breast cancer (TNBC) patients. Features are derived from tumor immune micro-environment and clinical data and used to train machine learning models to accurately predict the response to NAC in breast cancer patients (HER2+ AUC = 0.8975; TNBC AUC = 0.7674). The results demonstrate that this method outperforms the results trained from features that were manually generated by pathologists. The developed image features and algorithms were further externally validated by independent cohorts, yielding encouraging results, especially for the HER2+ subtype.

Embelin alleviates weaned piglets intestinal inflammation and barrier dysfunction via PCAF/NF-κB signaling pathway in intestinal epithelial cells.

BACKGROUND: Intestinal barrier plays key roles in maintaining intestinal homeostasis. Inflammation damage can severely destroy the intestinal integrity of mammals. This study was conducted to investigate the protective effects of embelin and its molecular mechanisms on intestinal inflammation in a porcine model. One hundred sixty 21-day-old castrated weaned pigs (Duroc × Landrace × Yorkshire, average initial body weight was 7.05 ± 0.28 kg, equal numbers of castrated males and females) were allotted to four groups and fed with a basal diet or a basal diet containing 200, 400, or 600 mg embelin/kg for 28 d. The growth performance, intestinal inflammatory cytokines, morphology of jejunum and ileum, tight junctions in the intestinal mucosa of piglets were tested. IPEC-1 cells with overexpression of P300/CBP associating factor (PCAF) were treated with embelin, the activity of PCAF and acetylation of nuclear factor-κB (NF-κB) were analyzed to determine the effect of embelin on PCAF/NF-κB pathway in vitro. RESULTS: The results showed that embelin decreased (P < 0.05) serum D-lactate and diamine oxidase (DAO) levels, and enhanced the expression of ZO-1, occludin and claudin-1 protein in jejunum and ileum. Moreover, the expression levels of critical inflammation molecules (interleukin-1ß, interleukin-6, tumor necrosis factor-α, and NF-κB) were down-regulated (P < 0.05) by embelin in jejunal and ileal mucosa. Meanwhile, the activity of PCAF were down-regulated (P < 0.05) by embelin. Importantly, transfection of PCAF siRNAs to IPEC-1 cell decreased NF-κB activities; embelin treatment downregulated (P < 0.05) the acetylation and activities of NF-κB by 31.7%-74.6% in IPEC-1 cells with overexpression of PCAF. CONCLUSIONS: These results suggested that embelin ameliorates intestinal inflammation in weaned pigs, which might be mediated by suppressing the PCAF/NF-κB signaling pathway.

Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. METHODS: Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. CONCLUSIONS: In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.

Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of finerenone and sodium-glucose cotransporter-2 inhibitors (SGLT2i) on reducing new-onset of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). METHOD: We searched the PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to April 30, 2022. Randomized control trials comparing finerenone or SGLT2i with placebo in patients with T2DM and CKD were selected. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: A total of 10 studies (35,841 patients) were included. Finerenone (RR 0.79, 95% CI 0.62-0.99) was associated with a decreased risk of AF compared with placebo, while SGLT2i were not. SGLT2i were associated with a decreased risk of hospitalization for heart failure (RR 0.78, 95% CI 0.63-0.98) compared with finerenone. They were comparable in AF(RR 0.84, 95% CI 0.48,1.46), major adverse cardiovascular events(MACE) (RR 0.93, 95% CI 0.81,1.06) and nonfatal stroke(RR 0.78, 95% CI 0.58,1.05). They both showed no significant risk of adverse events compared with placebo. CONCLUSION: There was no significant difference in the reduction of new-onset of atrial fibrillation between Finerenone and SGLT2i based on the indirect comparisons of currently available clinical studies. The large-sampled head-to-head trials was needed for the more precise conclusion.

Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials.

Objectives: To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin. Results: Forty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), P < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), P < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), P < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), P < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations. Conclusion: Statins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].

Serum Cannabinoid 24 h and 1 Week Steady State Pharmacokinetic Assessment in Cats Using a CBD/CBDA Rich Hemp Paste.

Hemp based cannabinoids have gained popularity in veterinary medicine due to the potential to treat pain, seizure disorders and dermatological maladies in dogs. Cat owners are also using hemp-based products for arthritis, anxiety and neoplastic disorders with no studies assessing hemp cannabinoids, namely cannabidiol efficacy, for such disorders. Initial twenty-four pharmacokinetic and chronic dosing serum concentration in cats are sparse. The aim of our study was to assess 8 cats physiological and 24 h and 1-week steady state pharmacokinetic response to a cannabidiol (CBD) and cannabidiolic acid (CBDA) rich hemp in a palatable oral paste. Using a standard dose of paste (6.4 mg/CBD + CBDA 5.3 mg/gram) across 8 cats weighing between 4.2 and 5.4 kg showed an average maximal concentration of CBD at 282.0 ± 149.4 ng/mL with a half-life of ~2.1 ± 1.1 h, and CBDA concentrations of 1,011.3 ± 495.4 ng/mL with a half-life of ~2.7 ± 1.4 h, showing superior absorption of CBDA. After twice daily dosing for 1 week the serum concentrations 6 h after a morning dosing showed that the acidic forms of the cannabinoids were approximately double the concentration of the non-acidic forms like CBD and Δ9- tetrahydrocannabinol (THC). The results of this study compared to two other recent studies suggest that the absorption in this specific paste product may be superior to oil bases used previously, and show that the acidic forms of cannabinoids appear to be absorbed better than the non-acidic forms. More importantly, physical and behavioral examinations every morning after dosing showed no adverse events related to neurological function or behavioral alterations. In addition, bloodwork after 1 week of treatment showed no clinically significant serum biochemical alterations as a reflection of hepatic and renal function all remaining within the reference ranges set by the diagnostic laboratory suggesting that short-term treatment was safe.

The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis.

Objective: The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or coronary heart disease. Methods: Randomized controlled trials were searched from PubMed, Embase, Cochrane Library, OpenGray, and ClinicalTrials.gov. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data extraction and synthesis. The pairwise meta-analysis compared statins and controls using a random-effects model, and a network meta-analysis compared the types and dosages of statins using the Bayesian random-effects model. The PROSPERO registration number is CRD42021242067. Results: The study included 37 randomized controlled trials with 17,410 participants and 20 interventions. According to the pairwise meta-analysis, statins significantly decreased CRP levels compared to controls (weighted mean difference [WMD] = -0.97, 95% confidence interval [CI] [-1.31, -0.64], P < 0.0001). In the network meta-analysis, simvastatin 40 mg/day appeared to be the best strategy for lowering CRP (Rank P = 0.18, WMD = -4.07, 95% CI = [-6.52, -1.77]). The same was true for the high-sensitivity CRP, non-acute coronary syndrome (ACS), <12 months duration, and clear measurement subgroups. In the CRP subgroup (rank P = 0.79, WMD = -1.23, 95% CI = [-2.48, -0.08]) and ≥12-month duration subgroup (Rank P = 0.40, WMD = -2.13, 95% CI = [-4.24, -0.13]), atorvastatin 80 mg/day was most likely to be the best. There were no significant differences in the dyslipidemia and ACS subgroups (P > 0.05). Node-splitting analysis showed no significant inconsistency (P > 0.05), except for the coronary heart disease subgroup. Conclusion: Statins reduced serum CRP levels in patients with dyslipidemia or coronary heart disease. Simvastatin 40 mg/day might be the most effective therapy, and atorvastatin 80 mg/day showed the best long-term effect. This study provides a reference for choosing statin therapy based on LDL-C and CRP levels.

Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway.

The efficacy of the sulforaphane derivative JY4 was evaluated in acute and chronic mouse models of ulcerative colitis induced by dextran sodium sulfate. Oral administration of JY4 led to significant improvements in symptoms, with recovery of body weight and colorectal length, together with reduced diarrhoea, bloody stools, ulceration of colonic tissue and infiltration of inflammatory cells. The oral bioavailability of JY4, determined by comparing oral dosing with injection into the tail vein, was 5.67%, which was comply with the idea in the intestinal function. Using a dual-luciferase reporter assay, immunofluorescence studies, western blot analysis and immunohistochemical staining, JY4 was shown to significant interfere with the NF-κB-p65 signaling pathway. By preventing the activation of NF-κB-p65, JY4 inhibited the overexpression of downstream inflammatory factors, thereby exerting an anti-inflammatory effect on the intestinal tract. This study thus provides a promising candidate drug, and a new concept for the treatment of ulcerative colitis.