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Background The rapid development of informatization in primary care in regions inhabited by ethnic minorities during the 13th Five-Year Plan period (2016—2020) , has laid a foundation for the improvement of the serving capacity of primary care supported by information technologies, but there is a lack of research on information technology and the efficiency of primary care. Objective To assess the status including effectiveness of informatization in primary care in China asregions inhabited by ethnic minorities, to explore the impact of information technology on improving the efficiency of primary care. Methods From July to October 2020, 84 primary care institutions in 23 ethnic counties in three autonomous prefectures of Sichuan (Ganzi, Liangshan and Aba) were selected by stratified sampling, and whose directors were invited to complete a self-administered questionnaire survey for understanding the status including effectiveness of informatization in their institutions. Furthermore, the heads of local health committees and directors of primary care institutions in these ethnic counties were invited to attend a group discussion regardingthe setting of departments, service development, status of informatization and settings for information services in primary care institutions. Results In terms of software construction, of the 84 primary care institutions, 57 (67.9%) used the public health system, 44 (52.4%) used the family doctor management system, and 25 (29.8%) use the hospital information system. Forty-seven (56.0%) primary care institutions had achieved vertical connectivity with other institutions (mostly regional- and county-level institutions as well as other members in a regional medical consortium) using information technologies, and regional informatization. Institutions that had horizontal connectivity with 69 (74.4%) of the primary care institutions were medical insurance departments. Only 18 (21.4%) institutions had independent information departments, and 34 (41.0%) did not employ information professionals. Lack of information professionals〔64 (76.2%) 〕, insufficient funds〔52 (61.9%) 〕 and weak infrastructure〔51 (60.7%) 〕 were main problems revealed in informatization construction. Institutions with regional informatization, vertical connectivity with other institutions, and the construction of a hospital information platform with electronic medical record system as the core were superior to those without in terms of setting of laboratory and examination departments and provision of traditional Chinese medicine services (P

The study of underwater vehicle wake detection is of significant importance within the field of target detection, localisation, and tracking of underwater vehicles. Given that propellers are the propellers of modern ships and underwater vehicles, the propeller wake field represents the principal target source for wake detection in underwater vehicles. The objective of this paper is to propose a method for measuring the wake of an underwater propeller based on a position-sensitive detector. A theoretical model of the relationship between the laser spot displacement and the change in the refractive index of the wake field is established on the basis of the principle of laser beam deflection. A prototype experimental setup for underwater propeller wake measurement was constructed based on the aforementioned optical measurement method. Furthermore, the simulation of the propeller wake flow field with strong density stratification and linear density stratification was conducted based on the experimental setup. Furthermore, experiments were conducted to detect the flow field of a propeller wake. The experimental results indicate that the wake dissipation times of the propeller in a strong density-stratified water environment are approximately 800 s and 750 s. Following the stabilisation of the wake field density, the laser spot position is observed to be stable at 0.341 mm and 0.441 mm, respectively, with a corresponding refractive index change of 2.99 × 10−6 RIU (refractive index unit) and 3.87 × 10−6 RIU, respectively. These experimental results are found to be in general agreement with the simulation results of the propeller wake field. A comparison of the experimental wake measurements based on the device with the wake measurements based on a CTD (conductivity–temperature–depth) device reveals a consistent trend. The realisation of this detection technique is of great significance for the advancement of research in the field of optical detection of underwater vehicle wake streams. [ABSTRACT FROM AUTHOR]

An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in β-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect β-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1– and Gal-9–presenting aEVs (PD-L1–Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1–Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1–Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual β-cell survival and mitigation of hyperglycemia. Article Highlights: Destruction of pancreatic β-cells by autoreactive CD4+ and CD8+ T cells is the main cause of type 1 diabetes (T1D); therefore, stunting autoreactive T cells is an effective strategy to alleviate T1D. Modulating the infiltration of T lymphocytes in the pancreas with exogenous programmed cell death ligand 1 (PD-L1) or galectin-9 (Gal-9) is an optimal treatment strategy for newly diagnosed T1D. PD-L1– and Gal-9–presenting (PD-L1–Gal-9) artificial extracellular vesicles (aEVs) exhibit characteristics of M2-type macrophages and efficaciously declined the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas. PD-L1–Gal-9 aEVs demonstrated immunosuppressive therapeutic effects and effectively alleviated hyperglycemia in NOD mice with new-onset T1D. [ABSTRACT FROM AUTHOR]

The seawater refractive index is an essential parameter in ocean observation, making its high-precision measurement necessary. This can be effectively achieved using a position-sensitive detector-based measurement system. However, in the actual measurement process, the impact of the jitter signal measurement error on the results cannot be ignored. In this study, we theoretically analysed the causes of long jitter signals during seawater refractive index measurements and quantified the influencing factors. Through this analysis, it can be seen that the angle between the two windows in the seawater refractive index measurement area caused a large error in the results, which could be effectively reduced by controlling the angle to within 2.06°. At the same time, the factors affecting the position-sensitive detector's measurement accuracy were analysed, with changes to the background light, the photosensitive surface's size, and the working environment's temperature leading to its reduction. To address the above factors, we first added a 0.9 nm bandwidth, narrow-band filter in front of the detector's photosensitive surface during system construction to filter out any light other than that from the signal light source. To ensure the seawater refractive index's measuring range, a position-sensitive detector with a photosensitive surface size of 4 mm × 4 mm was selected; whereas, to reduce the working environment's temperature variation, we partitioned the measurement system. To validate the testing error range of the optimised test system, standard seawater samples were measured under the same conditions, showing a reduction in the measurement system's jitter signal from 0.0022 mm to 0.0011 mm, before and after optimisation, respectively, as well as a reduction in the refractive index's deviation. The experimental results show that the refractive index of seawater was effectively reduced by adjusting the measurement system's optical path and structure. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on paroxysmal nocturnal haemoglobinuria (PNH), a rare blood disorder. The study used single-cell sequencing to analyze bone marrow cells from PNH patients and healthy controls. The researchers discovered alterations in the differentiation of bone marrow haematopoietic cells in PNH patients, which may contribute to the development of the disorder. The article includes clinical data on four PNH patients and discusses the mechanisms involved in PNH. The study highlights the differences in bone marrow cells between PNH patients and healthy individuals, providing insights into the impact of PNH on the distribution and function of hematopoietic cells in the bone marrow. [Extracted from the article]

Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is a disorder resulting from erythrocyte membrane deficiencies caused by PIG‐A gene mutations. While current treatments alleviate symptoms, they fail to address the underlying cause of the disease—the pathogenic PNH clones. In this study, we found that the expression of carbamoyl phosphate synthetase 1 (CPS1) was downregulated in PNH clones, and the level of CPS1 was negatively correlated with the proportion of PNH clones. Using PIG‐A knockout K562 (K562 KO) cells, we demonstrated that CPS1 knockdown increased cell proliferation and altered cell metabolism, suggesting that CPS1 participates in PNH clonal proliferation through metabolic reprogramming. Furthermore, we observed an increase in the expression levels of the histone demethylase JMJD1C in PNH clones, and JMJD1C expression was negatively correlated with CPS1 expression. Knocking down JMJD1C in K562 KO cells upregulated CPS1 and H3K36me3 expression, decreased cell proliferation and increased cell apoptosis. Chromatin immunoprecipitation analysis further demonstrated that H3K36me3 regulated CPS1 expression. Finally, we demonstrated that histone demethylase inhibitor JIB‐04 can suppressed K562 KO cell proliferation and reduced the proportion of PNH clones in PNH mice. In conclusion, aberrant regulation of the JMJD1C‐H3K36me3‐CPS1 axis contributes to PNH clonal proliferation. Targeting JMJD1C with a specific inhibitor unveils a potential strategy for treating PNH patients. [ABSTRACT FROM AUTHOR]

The mechanism underlying autophagy in paroxysmal nocturnal hemoglobinuria (PNH) remains largely unknown. We previously sequenced the entire genome exon of the CD59– cells from 13 patients with PNH and found genes such as CUX1 encoding Cut-like homeobox 1. Peripheral blood samples from 9 patients with PNH and 7 healthy control subjects were obtained to measure CUX1 expression. The correlation between CUX1 messenger RNA expression and PNH clinical indicators was analyzed. To simulate CUX1 expression in patients with PNH, we generated a panel of PNH cell lines by knocking out PIGA in K562 cell lines and transfected lentivirus with CUX1. CCK-8 and EDU assay assessed cell proliferation. Western blotting was used to detect Beclin-1, LC3A, LC3B, ULK1, PI3K, AKT, p-AKT, mTOR, and p-mTOR protein levels. Autophagosomes were observed with transmission electron microscopy. Chloroquine was used to observe CUX1 expression in PNH after autophagy inhibition. Leukocytes from patients with PNH had lower levels of CUX1 messenger RNA expression and protein content than healthy control subjects. The lactose dehydrogenase level and the percentage of PNH clones were negatively correlated with CUX1 relative expression. We reduced CUX1 expression in a PIGA knockout K562 cell line, leading to increased cell proliferation. Levels of autophagy markers Beclin-1, LC3B, LC3A, and ULK1 increased, and autophagosomes increased. Furthermore, PI3K/AKT/mTOR protein phosphorylation levels were lower. CUX1 expression did not change and cell proliferation decreased in CUX1 knocked down PNH cells after inhibition of autophagy by chloroquine. In brief, CUX1 loss-of-function mutation resulted in stronger autophagy in PNH. [ABSTRACT FROM AUTHOR]

The refractive index of seawater is one of the essential parameters in ocean observation, so it is necessary to achieve high-precision seawater refractive index measurements. In this paper, we propose a method for measuring the refractive index of seawater, based on a position-sensitive detector (PSD). A theoretical model was established to depict the correlation between laser spot displacement and refractive index change, utilizing a combination of a position-sensitive detector and laser beam deflection principles. Based on this optical measurement method, a seawater refractive index measurement system was established. To effectively enhance the sensitivity of refractive index detection, a focusing lens was incorporated into the optical path of the measuring system, and simulations were conducted to investigate the impact of focal length on refractive index sensitivity. The calibration experiment of the measuring system was performed based on the relationship between the refractive index of seawater and underwater pressure (depth). By measuring laser spot displacement at different depths, changes in displacement, with respect to both refractive index and depth, were determined. The experimental results demonstrate that the system exhibits a sensitivity of 9.93 × 10 − 9   R I U (refractive index unit), and the refractive index deviation due to stability is calculated as ± 7.54 × 10 − 9   R I U . Therefore, the feasibility of this highly sensitive measurement of seawater refractive index is verified. Since the sensitivity of the refractive index measurement of this measurement system is higher than the refractive index change caused by the wake of underwater vehicles, it can also be used in various applications for underwater vehicle wake measurement, as well as seawater refractive index measurement, such as the motion state monitoring of underwater navigation targets such as AUVs and ROVs. [ABSTRACT FROM AUTHOR]

Neuroglial cells have a high level of plasticity, and many types of these cells are present in the nervous system. Neuroglial cells provide diverse therapeutic targets for neurological diseases and injury repair. Cell reprogramming technology provides an efficient pathway for cell transformation during neural regeneration, while transcription factor-mediated reprogramming can facilitate the understanding of how neuroglial cells mature into functional neurons and promote neurological function recovery.

Most vaccines are designed to attack tumor cells by activating CD4+/CD8+αβ T cells. Unfortunately, αβ T cells, which only recognize the peptide antigens in the complexes with polymorphic MHCI/II molecules, surrender to the tumor heterogenicity. As another subset of T cells, γδ T cells become salient in antitumor because of their unique immunotherapeutic roles. Herein, a tumor vaccine is developed with multivalent antigens by fusion of tumor cell membranes with lipids and successfully activated γδ T cells via microneedle inoculation. It is certified that the evoked γδ T cells synchronize with αβ T cells revitalizing tumor‐induced immunotolerance. In turn, the tumors of mice are significantly inhibited and their median survival time is prolonged considerably. Moreover, the nanovaccine inhibits tumor recurrence after resection. The therapeutic effects are corroborated with the results from TCRδ−/− mice as well as cytokine expression in tumor. [ABSTRACT FROM AUTHOR]

The refractive index measurement of seawater has proven significance in oceanography, while an optical heterodyne interferometer is an important, highly accurate, tool used for seawater refractive index measurement. However, for practical seawater refractive index measurement, the refractive index of seawater needs to be monitored for long periods of time, and the influence of drift error on the measurement results for these cases cannot be ignored. This paper proposes a drift error compensation algorithm based on wavelet decomposition, which can adaptively separate the background from the signal, and then calculate the frequency difference to compensate for the drift error. It is suitable for unstable signals, especially signals with large differences between the beginning and the end, which is common in actual seawater refractive index monitoring. The authors identify that the primary cause of drift error is the frequency instability of the acousto-optic frequency shifter (AOFS), and the actual frequency difference was measured through experimentation. The frequency difference was around 0.1 Hz. Simulation experiments were designed to verify the effectiveness of the algorithm, and the standard deviation of the optical length of the results was on the scale of 10−8 m. Liquid refractive index measurement experiments were carried out in a laboratory, and the measurement error was reduced from 36.942% to 0.592% after algorithm processing. Field experiments were carried out regarding seawater refractive index monitoring, and the algorithm-processing results are able to match the motion of the target vehicle. The experimental data were processed with different algorithms, and, according to the comparison of the results, the proposed algorithm performs better than other existing drift error elimination algorithms. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a temporary incurable inflammatory bowel disease. Alpinia oxyphylla fructus polysaccharides (AOFPs) have anti-inflammatory, antioxidant, and other biological activities. In order to explore the therapeutic effect of AOFPs on UC, this study used deionized water, NaCl, HCl, and NaOH to extract AOFPs, and their protective effects on UC were evaluated by dextran sulfate sodium-induced UC mouse model. The results showed that extraction solvents had significant effects on the yield, molecular weights, monosaccharide compositions, total sugar contents, uronic acid contents, protein contents, and surface morphology of AOFPs. Histopathological analysis found that AOFPs could significantly reduce inflammatory cell infiltration and improve crypt morphology. ELISA and real-time PCR results show that AOFPs can downregulate the contents of TNF-α, IL-1β, and IL-6 and upregulate the content of IL-10. Western blot results show that AOFPs could enhance the expression of E-cadherin, occludin, claudin 1, and ZO-1. In addition, AOFPs improved the richness and diversity of intestinal flora and reshaped the intestinal flora by increasing the proportion of beneficial bacteria and inhibiting the proportion of harmful bacteria. These results indicate that AOFPs have therapeutic effects on UC. This may be due to the regulatory effect of AOFPs on the intestinal flora, restoring intestinal inflammation and permeability. [ABSTRACT FROM AUTHOR]

Watermelon frost, a traditional Chinese medicine produced using watermelon and Glauber's salt, has been widely used for the therapy of oral and throat disorders. Watermelon contains various phytochemical compounds including cucurbitacins and their glycoside derivatives, which have attracted considerable attention because of their medicinal values. However, whether the composition of cucurbitacins existed in watermelon frost was rarely reported. In this study, three cucurbitacins including cucurbitacin B, isocucurbitacin B, and cucurbitacin E were found from watermelon frost extract assisted by ultra‐high‐performance liquid chromatography‐tandem mass spectrometry and molecular networking guided strategy, and the compounds were verified using standard solutions. Furthermore, a quantification method for simultaneously targeted analysis of cucurbitacins was established using ultra‐high‐performance liquid chromatography‐tandem mass spectrometry operating in the multiple reaction monitoring mode. Among them, cucurbitacin B and cucurbitacin E in watermelon frost samples were determined, and the concentrations were 3.78 ± 0.18 and 0.86 ± 0.19 ng/ml, respectively. While isocucurbitacin B was not detected due to the lower content possibly. In conclusion, ultra‐high‐performance liquid chromatography‐tandem mass spectrometry combined with molecular networking is a very useful technique for the rapid identification of unknown cucurbitacin components in watermelon frost. [ABSTRACT FROM AUTHOR]