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Background Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases.Methods Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink’s panels.Results A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72).Conclusions Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study.Trial registration ClinicalTrials.gov identifier: NCT04211090.

Abstract Background Exposure to bisphenol A (BPA), an environmental pollutant known for its endocrine-disrupting properties, during gestation has been reported to increase the risk of fetal growth restriction (FGR) in an ovine model of pregnancy. We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta, oxidative stress, inflammatory responses, autophagy and endoplasmic reticulum stress (ERS). However, precise mechanisms underlying the BPA-induced placental dysfunction, and subsequently, FGR, as well as the potential involvement of placental ERS in these complications, remain to be investigated. Methods In vivo experiment, 16 twin-pregnant (from d 40 to 130 of gestation) Hu ewes were randomly distributed into two groups (8 ewes each). One group served as a control and received corn oil once a day, whereas the other group received BPA (5 mg/kg/d as a subcutaneous injection). In vitro study, ovine trophoblast cells (OTCs) were exposed to 4 treatments, 6 replicates each. The OTCs were treated with 400 μmol/L BPA, 400 μmol/L BPA + 0.5 μg/mL tunicamycin (Tm; ERS activator), 400 μmol/L BPA + 1 μmol/L 4-phenyl butyric acid (4-PBA; ERS antagonist) and DMEM/F12 complete medium (control), for 24 h. Results In vivo experiments, pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency, progesterone (P4) level and fetal weight, and an increase in placental estrogen (E2) level, together with barrier dysfunctions, OS, inflammatory responses, autophagy and ERS in type A cotyledons. In vitro experiment, the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy, ERS, pro-apoptosis and inflammatory response, and a decrease in the P4 level and the related protein and gene expressions of antioxidant, anti-apoptosis and barrier function. Moreover, treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine (the increased E2 level and decreased P4 level), OS, inflammatory responses, autophagy, and ERS. However, treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above. Conclusions In general, the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs, and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine, OS, inflammatory responses, and autophagy. These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Previous studies have revealed that dietary N-carbamylglutamate (NCG) or L-arginine (Arg) improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation (IUGR). Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown. This study, therefore, aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status, apoptosis and endoplasmic reticulum (ER) stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs. Forty-eight 7-d old Hu lambs, including 12 with normal birth weight (4.25 ± 0.14 kg) and 36 with IUGR (3.01 ± 0.12 kg), were assigned to 4 treatment groups (n = 12 each; 6 males and 6 females) for 3 weeks. The treatment groups were control (CON), IUGR, IUGR + Arg and IUGR + NCG. Relative to IUGR lambs, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content, as well as proliferation index, were higher (P

Bisphenol A (BPA)-induced oxidative stress (OS) and its potentially associated autophagy and apoptosis have not been studied previously in pregnant ewes. Accordingly, this study investigated the underlying mechanisms of BPA-induced autophagy and apoptosis in the placenta and primary trophoblasts of pregnant ewes exposed to BPA both in vivo and in vitro. In vivo experiment, pregnant Hu ewes (n = 8) were exposed to 5 mg/kg/d of BPA compared to control ewes (n = 8) receiving only corn oil from day 40 through day 110 of gestation. Exposure to BPA during gestation resulted in placental insufficiency, fetal growth restriction (FGR), autophagy, endoplasmic reticulum stress (ERS), mitochondrial dysfunction, OS, and apoptosis in type A placentomes. Regarding in vitro model, primary ovine trophoblasts were exposed to BPA, BPA plus chloroquine (CQ; an autophagy inhibitor) or BPA plus rapamycin (RAP; an autophagy activator) for 12 h. Data illustrated that exposure to BPA enhanced autophagy (ULK1, Beclin-1, LC3, Parkin, and PINK1), ERS (GRP78, CHOP10, ATF4, and ATF6) and apoptosis (Caspase 3, Bcl-2, Bax, P53) but decreased the antioxidant (CAT, Nrf2, HO-1, and NQO1)-related mRNA and protein expressions as well as impaired the mitochondrial function. Moreover, treatment with CQ exacerbated the BPA-mediated OS, mitochondrial dysfunction, apoptosis, and ERS. On the contrary, RAP treatment counteracted the BPA-induced trophoblast dysfunctions mentioned above. Overall, the findings illustrated that BPA exposure could contribute to autophagy in the ovine placenta and trophoblasts and that autophagy, in turn, could alleviate BPA-induced apoptosis, mitochondrial dysfunction, ERS, and OS. These results offer new mechanistic insights into the role of autophagy in mitigating BPA-induced placental dysfunctions and FGR.

In order to accomplish accurate mushroom classification and measurement, it is necessary to optimize the existing classification algorithm and measurement devices, as well as to design a specific robot to improve classification accuracy and measurement efficiency. In order to achieve the above objectives, a research-level verification of mushroom grading using Yolov5 + OpenCV and a mushroom measuring system using a resistance strain gauge sensor was carried out. In the aspect of mushroom grading, a method based on the OpenCV visual library was used to identify the minimum quadrilateral outside the mushroom contour, allowing the size of the mushroom to be measured. The experiment’s results show that the method can assess target objects that are occluded with each other under different illumination conditions with 96% accuracy. In the measurement of mushrooms, the strain of the resistance is converted into an analog signal, and the weight of different grades of mushrooms is converted according to the linear relationship after processing by the detection circuit module. Through this method, the error range is successfully controlled within ±0.02 kg, which meets the requirements of accurate measurement of mushrooms. The results of field experiments show that the proposed accurate grading and measurement method of Lentinula edodes is effective and feasible, and provides technical support for the intelligent grading and measurement of Lentinula edodes in production units.

This paper proposes a method for automatic pig detection and segmentation using RGB-D data for precision livestock farming. The proposed method combines the enhanced YOLOv5s model with the Res2Net bottleneck structure, resulting in improved fine-grained feature extraction and ultimately enhancing the precision of pig detection and segmentation in 2D images. Additionally, the method facilitates the acquisition of 3D point cloud data of pigs in a simpler and more efficient way by using the pig mask obtained in 2D detection and segmentation and combining it with depth information. To evaluate the effectiveness of the proposed method, two datasets were constructed. The first dataset consists of 5400 images captured in various pig pens under diverse lighting conditions, while the second dataset was obtained from the UK. The experimental results demonstrated that the improved YOLOv5s_Res2Net achieved a mAP@0.5:0.95 of 89.6% and 84.8% for both pig detection and segmentation tasks on our dataset, while achieving a mAP@0.5:0.95 of 93.4% and 89.4% on the Edinburgh pig behaviour dataset. This approach provides valuable insights for improving pig management, conducting welfare assessments, and estimating weight accurately.

Environmental cadmium (Cd) exposure has been associated with severe liver injury. In contrast, melatonin (Mel) is a candidate drug therapy for Cd-induced liver injury due to its diverse hepatoprotective activities. However, the precise molecular mechanism by which Mel alleviates the Cd-induced liver injury, as well as the Mel–gut microbiota interaction in liver health, remains unknown. In this study, mice were given oral gavage CdCl2 and Mel for 10 weeks before the collection of liver tissues and colonic contents. The role of the gut microbiota in Mel’s efficacy in alleviating the Cd-induced liver injury was evaluated by the gut microbiota depletion technique in the presence of antibiotic treatment and gut microbiota transplantation (GMT). Our results revealed that the oral administration of Mel supplementation mitigated liver inflammation, endoplasmic reticulum (ER) stress and mitophagy, improved the oxidation of fatty acids, and counteracted intestinal microbial dysbiosis in mice suffering from liver injury. It was interesting to find that neither Mel nor Cd administration induced any changes in the liver of antibiotic-treated mice. By adopting the GMT approach where gut microbiota collected from mice in the control (CON), Cd, or Mel + Cd treatment groups was colonized in mice, it was found that gut microbiota was involved in Cd-induced liver injury. Therefore, the gut microbiota is involved in the Mel-mediated mitigation of ER stress, liver inflammation and mitophagy, and the improved oxidation of fatty acids in mice suffering from Cd-induced liver injury.

Pork accounts for an important proportion of livestock products. For pig farming, a lot of manpower, material resources and time are required to monitor pig health and welfare. As the number of pigs in farming increases, the continued use of traditional monitoring methods may cause stress and harm to pigs and farmers and affect pig health and welfare as well as farming economic output. In addition, the application of artificial intelligence has become a core part of smart pig farming. The precision pig farming system uses sensors such as cameras and radio frequency identification to monitor biometric information such as pig sound and pig behavior in real-time and convert them into key indicators of pig health and welfare. By analyzing the key indicators, problems in pig health and welfare can be detected early, and timely intervention and treatment can be provided, which helps to improve the production and economic efficiency of pig farming. This paper studies more than 150 papers on precision pig farming and summarizes and evaluates the application of artificial intelligence technologies to pig detection, tracking, behavior recognition and sound recognition. Finally, we summarize and discuss the opportunities and challenges of precision pig farming.

L-arginine (Arg) is a semiessential amino acid with several physiological functions. N-Carbamylglutamate (NCG) can promote the synthesis of endogenous Arg in mammals. However, the roles of Arg or NCG on hepatic inflammation and apoptosis in suckling lambs suffering from intrauterine growth restriction (IUGR) are still unclear. The current work is aimed at examining the effects of dietary Arg and NCG on inflammatory and hepatocyte apoptosis in IUGR suckling lambs. On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 432 twin lambs. Normal-birthweight and IUGR Hu lambs were allocated randomly (n=12/group) to control (CON), IUGR, IUGR+1% Arg, or IUGR+0.1% NCG groups. Lambs were fed for 21 days from 7 to 28 days old. Compared with CON lambs, relative protein 53 (P53), apoptosis antigen 1 (Fas), Bcl-2-associated X protein (Bax), caspase-3, cytochrome C, tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB) p65, and NF-κB pp65 protein levels were higher (P

Background. An assessment of functional gastrointestinal disorders (FGIDs) in premature infants in their first year of life and neonatal factors influencing the progression of FGIDs was conducted in this research. Methods. Subjects selected for the retrospective study involved preterm infants being hospitalized in the neonatal department of Northern Jiangsu People's Hospital from September 2018 to September 2021. Data on neonatal risk factors such as gestational age, gender, birth weight, mode of delivery, feeding pattern, antibiotic administration and addition of probiotics, duration of hospitalization, maternal history of smoking, and mental health status, were all collected and analyzed. FGIDs were diagnosed according to Rome IV criteria. Results. This study included 988 preterm infants, with 725 (73.4%) having at least one FGID, 449 (45.4%) with infant colic, 411 (41.6%) with infant regurgitation, 237 (24.0%) with infant dyschezia, 190 (19.2%) with functional constipation, and 34 (3.4%) with functional diarrhea throughout the first year of life. In total, 263 infants (26.6%) without FGID symptoms were included in the control group. Further, a higher prevalence of FGIDs was observed in preterm infants with infant colic as well as infant regurgitation in particular as being characterized by a low gestational age (<32 w), low birth weight (<1.5 kg), Cesarean section, formula feeding, neonatal antibiotics use, hospitalization longer than 7 days, and maternal history of smoking. It was found from association analyses that infants exclusively breastfed in their first month of life were at lower risk for regurgitation than those in the control group. Conclusions. Unnecessary antibiotic use in the neonatal period, Cesarean delivery, passive smoking, lack of breastfeeding along with inappropriate probiotics usage are major risk factors for FGIDs, and their systematic control may be effective in reducing the susceptibility to and prevalence of FGIDs in preterm infants in the first year of life. [ABSTRACT FROM AUTHOR]

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Current methods for estimation of age- and year-specific instantaneous mortality rates based on multiyear, multiple-age tagging studies assume that it is feasible to tag fish in a wide range of ages. For some species, however, only the youngest one or two age-classes are readily available for tagging. Given the practical advantages of tagging young fish only, an important question is whether such studies would provide the information needed for estimation of age-dependent mortality rates. We investigated three designs: tagging only the youngest available age-class, tagging the two youngest age-classes, and tagging the first five age-classes. We carried out simulation studies to assess estimator performance under these three designs, in each case assuming the same total number of tagged fish. Data were generated assuming fishing mortality rates to be age and year dependent and natural mortality rates to be constant or with limited age dependence. Estimator performance is best when fish are tagged in five age-classes, and tagging fish in the two youngest age-classes shows substantial improvement compared with tagging one age-class only. External information about the tag-reporting rate is necessary to obtain estimators with reasonable properties, especially in the case of models with age-dependent natural mortality. Such information can be obtained from auxiliary studies by means of high-reward tags or planted tags. Collecting recovery information for several additional years after the last release produces small improvements in precision and bias. If tagging fish in multiple age-classes is impractical, reasonable precision can be obtained by tagging one or preferably two age-classes and obtaining supplemental information on the reporting rate. For illustration, estimates of age-dependent fishing and natural mortality rates were obtained from tag returns on Chesapeake Bay striped bass Morone saxatilis tagged at ages 3 and 4 years. [ABSTRACT FROM AUTHOR]

Catch-and-release fisheries have become very important in the management of overexploited recreational fish stocks. Tag return studies, where the tag is removed regardless of fish disposition, have been used to assess the effectiveness of restoration efforts for these fisheries. We extend the instantaneous rate formulation of tag return models to allow for catch and release as well as harvest. The key point of our methods is that, given an estimate of the tag reporting rate, the fishing mortality rate (F) is separated into two components: the mortality on harvested fish and the "mortality" on tags (because the tags are removed) of fish released alive. The total fishing mortality rate for untagged fish is the sum of the Fs due to harvest and hooking mortality suffered by fish released alive. Natural mortality rates can also be estimated. Both age-independent models and age-dependent models are constructed, and the age-dependent models are illustrated by application to data from a study of striped bass Morone saxatilis in Chesapeake Bay from 1991 to 2003 by the Maryland Department of Natural Resources. By fitting models of the natural mortality rate with limited age and year dependence, we demonstrate an overall decrease in natural mortality rates as fish age and provide evidence of an increase in natural mortality beginning in the late 1990s, when an outbreak of the disease mycobacteriosis is thought to have begun. Our results indicate that fishing mortality is age dependent; selectivity increases up to age 6, when fish appear to be fully recruited to the fishery. There is also evidence of an increase in fishing mortality since 1995, when regulations were relaxed. [ABSTRACT FROM AUTHOR]

Background For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal–bolus insulin regimen is often recommended. We aimed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes. Methods We did this 52 week, randomised, open-label, phase 3, non-inferiority trial at 105 study sites in 15 countries. Patients (aged ≥18 years) with type 2 diabetes inadequately controlled with conventional insulin treatment were randomly assigned (1:1:1), via a computer-generated randomisation sequence with an interactive voice-response system, to receive once-weekly dulaglutide 1·5 mg, dulaglutide 0·75 mg, or daily bedtime glargine. Randomisation was stratified by country and metformin use. Participants and study investigators were not masked to treatment allocation, but were unaware of dulaglutide dose assignment. The primary outcome was a change in glycated haemoglobin A1c (HbA1c) from baseline to week 26, with a 0·4% non-inferiority margin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01191268. Findings Between Dec 9, 2010, and Sept 21, 2012, we randomly assigned 884 patients to receive dulaglutide 1·5 mg (n=295), dulaglutide 0·75 mg (n=293), or glargine (n=296). At 26 weeks, the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg (−1·64% [95% CI −1·78 to −1·50], −17·93 mmol/mol [−19·44 to −16·42]) and dulaglutide 0·75 mg (−1·59% [−1·73 to −1·45], −17·38 mmol/mol [−18·89 to −15·87]) than in those receiving glargine (−1·41% [−1·55 to −1·27], −15·41 mmol/mol [−16·92 to −13·90]). The adjusted mean difference versus glargine was −0·22% (95% CI −0·38 to −0·07, −2·40 mmol/mol [–4·15 to −0·77]; p=0·005) for dulaglutide 1·5 mg and −0·17% (–0·33 to −0·02, −1·86 mmol/mol [–3·61 to −0·22]; p=0·015) for dulaglutide 0·75 mg. Five (<1%) patients died after randomisation because of septicaemia (n=1 in the dulaglutide 1·5 mg group); pneumonia (n=1 in the dulaglutide 0·75 mg group); cardiogenic shock; ventricular fibrillation; and an unknown cause (n=3 in the glargine group). We recorded serious adverse events in 27 (9%) patients in the dulaglutide 1·5 mg group, 44 (15%) patients in the dulaglutide 0·75 mg group, and 54 (18%) patients in the glargine group. The most frequent adverse events, arising more often with dulaglutide than glargine, were nausea, diarrhoea, and vomiting. Interpretation Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment. INSET: Panel: Research in context.. [ABSTRACT FROM AUTHOR]