Assessment of internal exposure risk from metals pollution of occupational and non-occupational populations around a non-ferrous metal smelting plant.

Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n=179) were significantly higher compared to controls (n=168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10-4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting.

Preoperative albumin-bilirubin score predicts short-term outcomes and long-term prognosis in colorectal cancer patients undergoing radical surgery.

BACKGROUND: The albumin-bilirubin (ALBI) score is a serum biochemical indicator of liver function and has been proven to have prognostic value in a variety of cancers. In colorectal cancer (CRC), a high ALBI score tends to be associated with poorer survival. AIM: To investigate the correlation between the preoperative ALBI score and outcomes in CRC patients who underwent radical surgery. METHODS: Patients who underwent radical CRC surgery between January 2011 and January 2020 at a single clinical center were included. The ALBI score was calculated by the formula (log10 bilirubin × 0.66) + (albumin × -0.085), and the cutoff value for grouping patients was -2.8. The short-term outcomes, overall survival (OS), and disease-free survival (DFS) were calculated. RESULTS: A total of 4025 CRC patients who underwent radical surgery were enrolled in this study, and there were 1908 patients in the low ALBI group and 2117 patients in the high ALBI group. Cox regression analysis revealed that age, tumor size, tumor stage, ALBI score, and overall complications were independent risk factors for OS; age, tumor stage, ALBI score, and overall complications were identified as independent risk factors for DFS. CONCLUSION: A high preoperative ALBI score is correlated with adverse short-term outcomes, and the ALBI score is an independent risk factor for OS and DFS in patients with CRC undergoing radical surgery.

Giant strong coupling in a Q-BICs' tetramer metasurface.

Due to their ultrahigh Q-factor and small mode volume, bound states in the continuum (BICs) are intriguing for the fundamental study of the strong coupling regime. However, the strong coupling generated by BICs in one metasurface is not always strong enough, which highly limits its efficiency in applications. In this work, we realize a giant strong coupling of at most 60 meV in a quasi-BICs' (Q-BICs) tetramer metasurface composed of four Si cylinders with two different sets of diagonal lengths. The Q-BICs are induced from two types of electric quadrupole (EQ), for which detuning can be flexibly controlled by manipulating the C4v symmetry breaking Δd. The giant Rabi splitting in our proposed metasurface performs more than 15 times of the previous works, which provides more possibilities for important nonlinear and quantum applications, such as nanolaser and quantum optics.

Glucose activated synergistic cascade therapy of diabetic wound by platinum and glucose oxidase decorated camelina lipid droplets.

Hyperglycemia provides a favorable breeding ground for bacteria, resulting in repeated and persistent inflammation of wounds and prolonged healing processes. In this study, platinum (Pt) nanoparticles (NPs) and glucose oxidase (GOx) were decorated on the surface of camelina lipid droplets (OB) linked with hFGF2, forming PGOB through in situ reduction of Pt ions and electrostatic adsorption, respectively. PGOB exhibits cascade enzyme catalytic activity, which can be activated by glucose in diabetic wound tissues. Specifically, GOx on PGOB catalyzes glucose into hydrogen peroxide, which can further decompose into hydroxyl radicals that have higher toxicity for bacterial inactivation. Additionally, glucose decomposition creates a low pH microenvironment, facilitating the cascade catalytic activity that ensures better bacterial suppression within the wound tissues. Furthermore, hFGF2 promotes the proliferation and migration of fibroblasts. Both in vitro and in vivo experiments confirm that PGOB effectively accelerates wound healing processes through bacteria inactivation and tissue regeneration. This study has developed an alternative strategy for glucose-triggered synergistic cascade therapy for diabetic wounds.

Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties as potent antibacterial agents against antibiotic-resistant bacteria.

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b showed high stability in the liver microsomes of rats and humans, along with acceptable tolerance in vitro and in vivo. Additionally, compound 16b exhibited promising efficacy in MRSA-infected mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria.

Inhibition of 5-HT alleviates PTSD-like behaviors and promotes hippocampal neuroplasticity by modulating hippocampal autophagy in rats.

5-hydroxytryptamine (5-HT) plays a substantial role in mitigating depression and anxiety. However, the potential effects of 5-HT against post-traumatic stress disorder (PTSD) and its underlying mechanisms remain unclear. Elevated Plus Maze test to evaluate anxiety-related behaviors, and the Open Field Test to assess overall activity levels and anxiety. Inflammatory cytokine levels were determined using ELISA. The levels of 5-HT and dopamine were measured using HPLC. mRNA and protein levels were examined by PCR and Western blot, respectively. Rats exposed to single prolonged stress (SPS) exhibited typical PTSD-like phenotypes, with decreased levels of 5-HT in the hippocampus and significant reductions in its downstream targets, brain-derived neurotrophic factor (BDNF) and TrkB. Additionally, it was discovered that the autophagy signaling pathway might be involved in regulating hippocampal BDNF in rats exposed to SPS. Subsequent treatment with an intracerebral injection of sh-SERT significantly inhibited anxiety and cognitive dysfunction in rats. Moreover, sh-SERT treatment was observed to substantially reverse the increase in autophagy signaling protein expression and consequently improve the expression of BDNF and TrkB proteins, which had been reduced. The current study demonstrates that sh-SERT exhibits significant anti-PTSD effects, potentially mediated in part through the reduction of cellular autophagy to enhance hippocampal synaptic plasticity.

Prospective, multicenter, self-controlled clinical trial on the effectiveness and safety of cable-transmission magnetically controlled capsule endoscope system for the examination of upper gastrointestinal diseases.

BACKGROUND AND AIMS: Many gastrointestinal (GI) disorders and precancerous conditions often present asymptomatically, leading to delayed patient diagnoses and treatment interventions. This study aimed to develop a novel cable-transmission magnetically controlled capsule endoscopy (CT-MCCE) system for detecting GI diseases and assess its safety and feasibility through clinical trials. METHODS: This prospective, multicenter, trial compared CT-MCCE with conventional gastroscopy in patients aged 18-75 years with upper GI diseases between October 2022 and May 2023. The primary endpoints included the evaluation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the detection of focal lesions within the esophagus, stomach, and duodenal bulb using CT-MCCE. RESULTS: A total of 180 individuals (mean age: 43.1 years, 52.22% female) were recruited from three hospitals in China. CT-MCCE detected lesions in esophagus with 97.22% sensitivity, 100% specificity, a PPV of 100%, a NPV of 98.18%, and 98.89% accuracy. CT-MCCE detected gastric focal lesions in the whole stomach with 96.81% sensitivity, 98.84% specificity, a PPV of 98.91%, a NPV of 96.59%, and 97.78% accuracy. CT-MCCE detected lesions in the duodenal bulb with 100% sensitivity, 100% specificity, a PPV of 100%, a NPV of 100%, and 100% accuracy. There were no significant differences between CT-MCCE and EGD regarding the cleanliness of the upper GI tract and visibility of the upper GI mucosa. However, CT-MCCE was associated with a lower incidence of discomfort than EGD (P<0.001). CONCLUSIONS: The diagnostic performance of CT-MCCE is comparable to that of EGD in the completion of upper GI tract examinations and lesion detection. Furthermore, the improved tolerance of CT-MCCE in detecting upper GI diseases was noted without any observed adverse events.

Effects of undescribed iridoids in Patrinia punctiflora on insulin resistance in HepG2 cells.

Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins PU (1-6). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p-AKT, GLUT4 and p-GSK3ß proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.

Silver diamine fluoride in preventing enamel erosion: An in vitro study with salivary pellicle.

OBJECTIVES: To compare the prevention of enamel erosion and discolouring effect with a single and two weekly topical applications of silver diamine fluoride (SDF) solution. METHODS: Human enamel blocks were divided into four groups. Group 1 (SDF2) received two weekly applications of SDF solution (Advantage Arrest: 260,000 ppm Ag, 44,300 ppm F, pH 9.1). Group 2 (SDF1) received a single application of SDF solution. Group 3 (SNF, Positive Control) received daily application of stannous-chloride/amine-fluoride/sodium-fluoride solution (Elmex® Enamel professional: 800 ppm Sn(II), 500 ppm F, pH 4.5). Group 4 (DW, Negative Control) received daily application of deionised water. The treated blocks were subjected to a 14-day erosive challenge. Crystal characteristics, elemental composition, surface morphology, percentage of surface microhardness loss (%SMHL), surface loss, and total colour change (ΔE) of the blocks were investigated using X-ray diffraction (XRD), energy-dispersive spectrometry (EDS) and scanning electron microscopy (SEM), Vickers' hardness testing, non-contact profilometry, and digital spectrophotometry, respectively. RESULTS: XRD and EDS revealed precipitates of silver for SDF2 and SDF1 and tin for SNF. SEM showed prominent etched enamel pattern on DW than the other three groups. The%SMHL (%) of SDF2, SDF1, SNF, and DW were 26.6 ± 2.9, 33.6 ± 2.8, 38.9 ± 2.9, and 50.5 ± 2.8 (SDF2SDF1=SNF>DW, p < 0.05). CONCLUSION: Two weekly applications was more effective than a single application of SDF in preventing enamel erosion, though it caused more discolouration. CLINICAL SIGNIFICANCE: Topical application of 38 % SDF with two weekly applications protocol is effective in preventing enamel erosion.

Targeted co-delivery of rapamycin and oxaliplatin by liposomes suppresses tumor growth and metastasis of colorectal cancer.

The activation of tumor cell immunogenicity through oxaliplatin (OXP)-induced immunogenic cell death (ICD) has significant implications in cancer treatment. However, the anti-tumor effect of OXP monotherapy still has many shortcomings, and the systemic administration of OXP leads to low drug concentration at the tumor site, which is susceptible to systemic toxic side effects. In this study, a combined therapeutic strategy using folate-modified nanoliposomes co-delivered with rapamycin (Rapa) and OXP (abbreviated as FA@R/O Lps) is proposed for the treatment of colorectal cancer (CRC). Rapa and OXP can directly inhibit tumor cell proliferation and induce apoptosis. OXP induces ICD by triggering the release of danger signals, such as HMGB1, ATP, and calreticulin. FA@R/O Lps with a particle size of about 134.1±1.8 nm and a small dispersion were successfully prepared. This novel liposomal system can be used to target and increase drug accumulation in tumors. In-vivo experiments showed that FA@R/O Lps successfully inhibit CRC growth and liver metastasis, and simultaneously reduce off-target toxicity. In particular, FA@R/O Lps showed greater therapeutic effects than free Rapa/OXP and R/O Lps. Taken together, this study provides a novel combination of Rapa and OXP, and a nano-delivery system for enhanced anti-CRC efficacy. The results suggest that FA@R/O Lps could be a promising strategy for the treatment of CRC.

A retrospective analysis of e-prescriptions for non-communicable diseases on a telehealth platform in Malaysia.

BACKGROUND: The management of non-communicable diseases (NCDs) has benefited from telehealth services. As these services which include teleconsultation services and e-prescriptions are relatively new in Malaysia, the data generated provide an unprecedented opportunity to study medication use patterns for the management of NCDs in the country. We analyze e-prescriptions from a local telehealth service to identify medication use patterns and potential areas to optimize medication use in relation to clinical practice guidelines. METHODS: A cross sectional observational study was conducted by retrieving e-prescription records retrospectively from a telehealth service. 739,482 records from January 2019 to December 2021 were extracted using a designated data collection form. Data cleaning, standardization and data analysis were performed using Python version 3.11. The diagnoses were classified according to the International Classification of Disease 10 (ICD-10), while medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Diagnoses, frequency of use for medication classes and individual medications were analyzed and compared to clinical practice guidelines. RESULTS: The top five NCD diagnoses utilized by the service were hypertension (37.7%), diabetes mellitus (25.1%), ischemic heart disease (24.3%), asthma (14.4%), and dyslipidemia (11.7%). Medications were prescribed mostly in accordance with guideline recommendations. However, angiotensin receptor blockers (ARBs) were significantly more frequently prescribed compared to angiotensin converting enzyme inhibitors (ACEIs). Several medication classes appeared underutilized, including ACEIs in hypertensive patients with diabetes or ischemic heart disease, sodium glucose cotransporter 2 inhibitors in diabetic patients with ischemic heart disease, and metformin in patients with diabetes. CONCLUSIONS: Telehealth services are currently being utilized for the management of NCDs. Medication use for the management of NCDs through these services are mostly in accordance with guideline recommendations, but there exist areas that would warrant further investigation to ensure optimal clinical and economic outcomes are achieved.

Development and Validation of a Stromal-Immune Signature to Predict Prognosis in Intrahepatic Cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Association between "weekend warrior" physical activity and the incidence of neurodegenerative diseases.

While guidelines recommend 150 â€‹min of moderate to vigorous physical activity (MVPA) weekly to enhance health, it remains unclear whether concentrating these activities into 1-2 days of the week, "weekend warrior" (WW) pattern, has the same benefit for neurodegenerative diseases (NDDs). This study aimed to evaluate the associations of WW pattern and the risk of NDDs. This prospective study was conducted using accelerometer-based physical activity data for a full week from June 2013 to December 2015 in the UK Biobank. These individuals were categorized into distinct physical activity patterns, including the WW pattern (i.e., over 50% or 75% of recommended MVPA achieved over 1-2 days), regular pattern, and inactive pattern. Cox proportional hazards model was used to evaluate the association between physical activity patterns and outcomes. Compared to inactive group, WW pattern and regular pattern was similarly linked to a reduced risk of all-cause dementia (WW: Hazard Ratio [HR]: 0.68, 95% Confidence Interval [CI]: 0.56-0.84; regular: HR: 0.86, 95% CI: 0.67-1.1) and all-cause Parkinsonism (WW: HR: 0.47, 95% CI: 0.35-0.63; regular: HR: 0.69, 95% CI: 0.5-0.95). When the exercise threshold was increased to 75% of MVPA, both patterns still were associated with decreased risk of incident all-cause dementia (WW: HR: 0.61, 95% CI: 0.41-0.91; regular: HR: 0.76, 95% CI: 0.63-0.92) and all-cause Parkinsonism (WW: HR: 0.22, 95% CI: 0.10-0.47; regular: HR: 0.59, 95% CI: 0.46-0.75). Concentrating recommended physical activities into 1-2 days per week is associated with a lower incidence of NDDs.

Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

Ultralow-Energy-Consumption Photosynaptic Transistor Utilizing Conjugated Polymers/Perovskite Quantum Dots Nanocomposites With Ligand Density Optimization.

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

Prognostic potential of neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in acute myocardial infarction patients combined with chronic obstructive pulmonary disease.

Background: Inflammation is considered to play an important role in chronic obstructive pulmonary disease (COPD) and acute myocardial infarction (AMI), but the relationship between inflammation and poor prognosis in these patients has not yet been studied. Methods: We enrolled AMI patients combined with COPD and divided them into three groups according to the tertiles of neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and monocyte to lymphocyte ratio (MLR) respectively. Logistic regression analyses were used to identify risk factors for in-hospital all-cause death in these patients. Covariates were adjusted stepwise to determine the association between inflammatory markers and poor prognosis. Also, the receiver operating characteristic (ROC) curve was used to evaluate the greatest predictive indicator for all-cause death. Results: A total of 281 AMI patients combined with COPD were enrolled, of which 31 experienced in-hospital mortality. The risk of all-cause death was significantly higher among those with higher NLR. The highest tertile of NLR was significantly associated with an increased risk of all-cause death (all P < 0.05). This association remained significant after adjusting for confounding factors [Odds Ratio (OR): 10.571, 95% confidence interval (CI): 2.307-48.442, P = 0.002]. Moreover, compared to MLR and PLR, NLR had the highest predictive value for all-cause death [area under the curve (AUC): 0.764, 95% CI: 0.681-0.847]. Conclusion: In AMI patients combined with COPD, elevated levels of inflammation were associated with increased all-cause mortality. Compared to other inflammatory indicators, NLR may provide a more superior predictive value.

Bamboo fiber improves piglet growth performance by regulating the microbial composition of lactating sows and their offspring piglets.

Introduction: Feeding bamboo powder is a kind of fiber raw material mainly composed of insoluble dietary fiber (IDF). In this study, IDF-based rice husk meal and feeding bamboo powder were used to compare the effects of bamboo fiber on fecal microflora and the performance of lactating sows and their offspring piglets. Methods: Thirty healthy crossbred gilts (Yorkshire × Landrace) at day 105 of gestation were randomly allocated into three groups: CON, TRE1 supplemented with 2% BBF1 (feeding bamboo powder), and TRE2 supplemented with 2% BBF2 (99% feeding bamboo powder +1% bamboo fiber polymer material). The reproductive performance, serum indexes, and fecal microbiota of sows and piglets were analyzed. The results showed that, compared with CON, the average feed intake of sows in TRE1 during the second week of lactation was significantly increased by 21.96% (p < 0.05), the average daily gain (ADG) per litter in TRE1 on 11-21 days and 3-21 days of lactation was significantly increased by 50.68 and 31.61%, respectively (p < 0.05), and the serum triglyceride content of sows in TRE1 on the 21st day of lactation was significantly increased (p < 0.05). The 16S rRNA analysis showed that dietary bamboo fiber significantly increased the fecal microbial richness index Ace, Chao, and Sobs of sows (p < 0.05) and tended to increase the Sobs index of suckling piglets on day 21 (p < 0.10). Compared with CON, BBF1 supplementation significantly decreased the abundance of Christensenellaceae_R-7_group in feces of sows on days 7 and 21 after delivery (p < 0.05), while BBF2 decreased the genera Christensenellaceae_R-7_group on days 7 (p < 0.10) and 21 (p < 0.05) after delivery. Spearman correlation analysis showed that the abundance of Phascolarctobacterium in the feces of piglets on the 21st day after delivery was significantly positively correlated with diarrhea rate and significantly negatively correlated with ADG per litter, day 21 litter weight, and 3- to 21-day survival rate. In contrast, Christensenellaceae_R-7_group was significantly negatively correlated with diarrhea rate and positively correlated with ADG per litter. Discussion: These results indicated that maternal BBF1 supplementation improved the litter weight gain of suckling piglets, which was associated with the improvement of diversity and structure of the fecal microbiota in the piglets.

An ex vivo method to evaluate vasoactivity induced by hemoglobin-based oxygen carriers in resistance vessels.

Red blood cell substitutes offer a solution to the problem of blood shortage and side effects of blood transfusion. Hemoglobin-based oxygen carriers (HBOCs) are one of the promising substitutes for red blood cells. Vasoactivity, which refers to the side effect of HBOCs that causes vasoconstriction and subsequent hypertension, limits the clinical application of HBOCs. In this study, an ex vivo method for the evaluation of vasoactivity induced by HBOCs was established based on isolated rat mesenteric artery vessels and the DMT120CP system. The DMT120CP system, equipped with a flowmeter, permits the control of intravascular pressure, pressure gradient, and flow conditions with high accuracy, simulating the physiological conditions for isolated vessels. The concentration of noradrenaline was optimized to 1 × 10-6∼3 × 10-6 M. PEGylated bovine hemoglobin (PEG-bHb) was synthesized and perfused into the vessel for vasoactivity evaluation, with bHb as the positive control and PSS buffer solution as the negative control. PEG-bHb showed a hydration diameter of 15.5 ± 1.4 nm and a P50 value of 6.99 mmHg. PEG-bHb exhibited a colloid osmotic pressure of 64.1 mmHg and a viscosity of 1.73 cp at 40 mg/mL. The established vasoactivity evaluation method showed significant differences in samples (bHb or PEG-bHb) with different vasoactivity properties. The vasoconstriction percentage induced by PEG-bHb samples synthesized in different batches showed coefficients of variation less than 5%, indicating good applicability and repeatability. The established evaluation method can be applied to study the vasoactivity induction and elimination strategies, promoting the clinical application of HBOCs.

Predictors of early colorectal cancer metastasis to lymph nodes: providing rationale for therapy decisions.

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.