Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Advances in Innate Immunity to Overcome Immune Rejection during Xenotransplantation.

Transplantation is an effective approach for treating end-stage organ failure. There has been a long-standing interest in xenotransplantation as a means of increasing the number of available organs. In the past decade, there has been tremendous progress in xenotransplantation accelerated by the development of rapid gene-editing tools and immunosuppressive therapy. Recently, the heart and kidney from pigs were transplanted into the recipients, which suggests that xenotransplantation has entered a new era. The genetic discrepancy and molecular incompatibility between pigs and primates results in barriers to xenotransplantation. An increasing body of evidence suggests that innate immune responses play an important role in all aspects of the xenogeneic rejection. Simultaneously, the role of important cellular components like macrophages, natural killer (NK) cells, and neutrophils, suggests that the innate immune response in the xenogeneic rejection should not be underestimated. Here, we summarize the current knowledge about the innate immune system in xenotransplantation and highlight the key issues for future investigations. A better understanding of the innate immune responses in xenotransplantation may help to control the xenograft rejection and design optimal combination therapies.

The importance of vitellogenin receptors in the oviposition of the pond wolf spider, Pardosa pseudoannulata.

Vitellogenin receptor (VgR) is crucial for vitellogenin (Vg) uptake by oocytes. VgR is less known in Arachnida, especially in spiders. Different from only one VgR in an arthropod species, two VgRs, VgR-1 and VgR-2, were found in the pond wolf spider, Pardosa pseudoannulata. Both VgRs had the typical domains of the low-density lipoprotein receptor family except for the absence of the ligand-binding domain 1 in VgR-2. Spatiotemporal expression profiles showed that two VgR genes were consistently highly expressed in females and their ovaries, but VgR-1 was 48-fold that of VgR-2 in ovaries. The transcriptional level of VgR-1 was significantly downregulated by RNAi, but it did not work for VgR-2 although several trials were performed. Vg-1 and Vg-2 might be the ligands of VgR-1 because their expressions were also decreased in the dsVgR-1-treated females. Silencing VgR-1 prolonged the pre-oviposition period by 56 h. The expression of VgRs and Vgs were upregulated by juvenile hormones (JHs), which suggested that JHs were the essential factors to vitellogenesis in the spider. The present study revealed the importance of VgR-1 in the spider oviposition, which will improve the understanding on VgR physiological functions in spiders.

ELASPIC2 (EL2): Combining Contextualized Language Models and Graph Neural Networks to Predict Effects of Mutations.

The ELASPIC web server allows users to evaluate the effect of mutations on protein folding and protein-protein interaction on a proteome-wide scale. It uses homology models of proteins and protein-protein interactions, which have been precalculated for several proteomes, and machine learning models, which integrate structural information with sequence conservation scores, in order to make its predictions. Since the original publication of the ELASPIC web server, several advances have motivated a revisiting of the problem of mutation effect prediction. First, progress in neural network architectures and self-supervised pre-trained has resulted in models which provide more informative embeddings of protein sequence and structure than those used by the original version of ELASPIC. Second, the amount of training data has increased several-fold, largely driven by advances in deep mutation scanning and other multiplexed assays of variant effect. Here, we describe two machine learning models which leverage the recent advances in order to achieve superior accuracy in predicting the effect of mutation on protein folding and protein-protein interaction. The models incorporate features generated using pre-trained transformer- and graph convolution-based neural networks, and are trained to optimize a ranking objective function, which permits the use of heterogeneous training data. The outputs from the new models have been incorporated into the ELASPIC web server, available at http://elaspic.kimlab.org.

Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study.

Following standard treatments, the traditional model for enhancing anti-tumor immunity involves performing immune reconstitution (e.g., adoptive immune cell therapies or immunoenhancing drugs) to prevent recurrence. For patients with advanced non-small cell lung cancer, we report here on two objectives, the immunosenescence for advanced non-small cell lung cancer and hydrogen gas inhalation for immune reconstitution. From July 1st to September 25th, 2019, 20 non-small cell lung cancer patients were enrolled to evaluate the immunosenescence of peripheral blood lymphocyte subsets, including T cell, natural killer/natural killer T cell and gamma delta T cell. Two weeks of hydrogen inhalation was performed during the waiting period for treatment-related examination. All patients inhaled a mixture of hydrogen (66.7%) and oxygen (33.3%) with a gas flow rate of 3 L/min for 4 hours each day. None of the patients received any standard treatment during the hydrogen inhalation period. After pretreatment testing, major indexes of immunosenescence were observed. The abnormally higher indexes included exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. The abnormally lower indexes included functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After 2 weeks of hydrogen therapy, all six cell subsets increased to within the normal range. The current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment can significantly improve most of these indexes. The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7th, 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24th, 2019.

Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.

Chemotherapy, targeted therapy, and immunotherapy are used against advanced non-small cell lung cancer. A clinically efficacious method for relieving the adverse events associated of such therapies is lacking. Fifty-eight adult patients were enrolled in our trial to relieve pulmonary symptoms or the adverse events of drugs. Twenty patients who refused drug treatment were assigned equally and randomly to a hydrogen (H2)-only group and a control group. According to the results of tumor-gene mutations and drug-sensitivity tests, 10, 18, and 10 patients were enrolled into chemotherapy, targeted therapy, and immunotherapy groups in which these therapies were combined with H2-therapy, respectively. Patients underwent H2 inhalation for 4-5 hours per day for 5 months or stopped when cancer recurrence. Before study initiation, the demographics (except for tumor-mutation genes) and pulmonary symptoms (except for moderate cough) of the five groups showed no significant difference. During the first 5 months of treatment, the prevalence of symptoms of the control group increased gradually, whereas that of the four treatment groups decreased gradually. After 16 months of follow-up, progression-free survival of the control group was lower than that of the H2-only group, and significantly lower than that of H2 + chemotherapy, H2 + targeted therapy, and H2 + immunotherapy groups. In the combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared. H2 inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications for patients with advanced non-small cell lung cancer. This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019.

"Real world survey" of hydrogen-controlled cancer: a follow-up report of 82 advanced cancer patients.

Advanced cancer treatment is a huge challenge and new ideas and strategies are required. Hydrogen exerts antioxidant and anti-inflammatory effects that may be exploited to control cancer, the occurrence and progression of which is closely related to peroxidation and inflammation. We conducted a prospective follow-up study of 82 patients with stage III and IV cancer treated with hydrogen inhalation using the "real world evidence" method. After 3-46 months of follow-up, 12 patients died in stage IV. After 4 weeks of hydrogen inhalation, patients reported significant improvements in fatigue, insomnia, anorexia and pain. Furthermore, 41.5% of patients had improved physical status, with the best effect achieved in lung cancer patients and the poorest in patients with pancreatic and gynecologic cancers. Of the 58 cases with one or more abnormal tumor markers elevated, the markers were decreased at 13-45 days (median 23 days) after hydrogen inhalation in 36.2%. The greatest marker decrease was in achieved lung cancer and the lowest in pancreatic and hepatic malignancies. Of the 80 cases with tumors visible in imaging, the total disease control rate was 57.5%, with complete and partial remission appearing at 21-80 days (median 55 days) after hydrogen inhalation. The disease control rate was significantly higher in stage III patients than in stage IV patients (83.0% and 47.7%, respectively), with the lowest disease control rate in pancreatic cancer patients. No hematological toxicity was observed although minor adverse reactions that resolved spontaneously were seen in individual cases. In patients with advanced cancer, inhaled hydrogen can improve patients' quality-of-life and control cancer progression. Hydrogen inhalation is a simple, low-cost treatment with few adverse reactions that warrants further investigation as a strategy for clinical rehabilitation of patients with advanced cancer. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval number: Fuda20181207).

Mesoproterozoic juvenile crust in microcontinents of the Central Asian Orogenic Belt: evidence from oxygen and hafnium isotopes in zircon.

We report in situ O and Hf isotope data of zircon grains from coeval Mesoproterozoic (ca. 1.4 Ga) igneous metamafic (amphibolite) and granitic rocks of the Chinese Central Tianshan microcontinent (CTM) in the southern Central Asian Orogenic Belt (CAOB). Zircon grains from amphibolite have mantle-like δ18OVSMOW values of 4.7-5.6‰ and juvenile Hf isotopic compositions (εHf(t) = 8.4-15.3; TDMC = 1.57-1.22 Ga), whereas those from granitic rocks have δ18OVSMOW values of 5.6-7.0‰ and evolved Hf isotopic compositions (εHf(t) = -1.0-8.2; TDMC = 2.09-1.62 Ga). Zircon O-Hf isotopic compositions of the metamafic and granitic rocks provide evidence for Mesoproterozoic (ca. 1.4 Ga) crustal growth and a substantial Palaeoproterozoic supracrustal component in the CTM. These findings and previous studies, reporting ca. 1.4 Ga magmatic rocks from other microcontinents of the CAOB, suggest that a large belt of Mesoproterozoic (ca. 1.4 Ga) juvenile continental crust formed in a continental terrane, fragments of which now occur over a distance of more than a thousand kilometres in the southern CAOB.