Dietary Bacillus velezensis KNF-209 supplementation improves growth performance, enhances immunity, and promotes gut health in broilers.

This study aimed to investigate the effects of dietary Bacillus velezensis KNF-209 (BV-KNF-209) on the growth performance, immunity, and gut health of broilers. A total of 540 one-day-old male Cobb-500 broilers were randomly divided into 5 groups of 6 replicates with 18 broilers per replicate. Dietary treatments were corn-soybean meal basal diets supplemented with 0, 50, 100, 200, and 400 mg/kg BV-KNF-209 (CON, BV 50, BV 100, BV 200, and BV 400 groups, respectively) for 42 d. Compared with the CON group, the average daily gains (ADG) at 0 to 42 d in the BV 100 and BV 200 groups were significantly increased (P < 0.01), and the feed-to-gain (F:G) ratios were significantly decreased at 0 to 21 d (P < 0.01) and 0 to 42 d (P < 0.05). The BV 200 and BV 400 groups had higher serum immunoglobulin M (IgM) levels at d 21 and 42 (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were significantly decreased in the BV 50, BV 100, and BV 200 groups at d 21 (P < 0.05), and serum IL-1ß and IL-6 levels were also reduced in the BV 100 and BV 200 groups at d 42 (P < 0.05). Meanwhile, increased interleukin-10 (IL-10) levels in the jejunal and ileal mucosa at d 42 were observed in the BV 100, BV 200, and BV 400 groups (P < 0.05), while the IL-1ß and IL-6 levels (P < 0.01) were decreased. The BV 200 and BV 400 groups showed significantly higher activities of lipase and trypsin (P < 0.05) in jejunal digesta as well as higher activities of amylase and trypsin (P < 0.01) in ileal digesta at d 42. The cecal acetic acid and propionic acid levels in the BV groups and lactic acid levels in the BV 50, BV 100, and BV 200 groups (P < 0.05) were significantly higher compared to those in the CON group. Overall, dietary BV-KNF-209 supplementation significantly improved broiler growth performance, an effect that may have been achieved by heightening immunity, increasing digestive enzyme activity, and raising intestinal short-chain fatty acids and lactic acid levels.

Latitudinal patterns and their climate drivers of the δ 13C, δ 15N, δ 34S isotope signatures of Spartina alterniflora across plant life-death status: a global analysis.

Isotopic signatures offer new methods, approaches, and perspectives for exploring the ecological adaptability and functions of plants. We examined pattern differences in the isotopic signatures (δ 13C, δ 15N, δ 34S) of Spartina alterniflora across varying plant life-death status along geographic clines. We extracted 539 sets of isotopic data from 57 publications covering 267 sites across a latitude range of over 23.8° along coastal wetlands. Responses of isotopic signatures to climate drivers (MAT and MAP) and the internal relationships between isotopic signatures were also detected. Results showed that the δ 13C, δ 15N, and δ 34S of S. alterniflora were -13.52 ± 0.83‰, 6.16 ± 0.14‰, and 4.01 ± 6.96‰, with a range of -17.44‰ to -11.00‰, -2.40‰ to 15.30‰, and -9.60‰ to 15.80‰, respectively. The latitudinal patterns of δ 13C, δ 15N, and δ 34S in S. alterniflora were shaped as a convex curve, a concave curve, and an increasing straight line, respectively. A decreasing straight line for δ 13C within the ranges of MAT was identified under plant life status. Plant life-death status shaped two nearly parallel decreasing straight lines for δ 34S in response to MAT, resulting in a concave curve of δ 34S for live S. alterniflora in response to MAP. The δ 15N of S. alterniflora significantly decreased with increasing δ 13C of S. alterniflora, except for plant death status. The δ 13C, δ 15N, and δ 34S of S. alterniflora are consistent with plant height, stem diameter, leaf traits, etc, showing general latitudinal patterns closely related to MAT. Plant life-death status altered the δ 15N (live: 6.55 ± 2.23‰; dead: -2.76 ± 2.72‰), latitudinal patterns of S. alterniflora and their responses to MAT, demonstrating strong ecological plasticity and adaptability across the geographic clines. The findings help in understanding the responses of latitudinal patterns of the δ 13C, δ 15N, and δ 34S isotope signatures of S. alterniflora in response plant life-death status, and provide evidence of robust ecological plasticity and adaptability across geographic clines.

Prediction of clinical risk assessment and survival in chronic obstructive pulmonary disease with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.

The role of adenoid immune phenotype in polysensitized children with allergic rhinitis and adenoid hypertrophy.

BACKGROUND: There is increasing interest in elucidating the relationship between adenoid hypertrophy (AH) and allergic rhinitis (AR). However, the impact of aeroallergen sensitization patterns on children with AH and AR remains unclear. METHODS: Patients aged 2-8 years (recruited from January 2019 to December 2022) with nasal symptoms were assessed for allergies, adenoid size, and respiratory viral infection history. The serum total immunoglobulin E (IgE) and specific IgE levels were measured, and flexible nasal endoscopy was performed. The relationship between AH, aeroallergen sensitization patterns, and lymphocyte subpopulations in adenoid samples was analyzed using flow cytometry. RESULTS: In total, 5281 children were enrolled (56.5% with AR; and 48.6% with AH). AH was more prevalent in children with AR. Compared to nonsensitized individuals, those polysensitized to molds had a higher prevalence of AH (adjusted OR 1.61, 95% CI 1.32-1.96) and a greater occurrence of two or more respiratory viral infections, particularly in adenoidectomy patients. The percentages and corrected absolute counts of regulatory T (Treg) cells, activated Tregs, class-switched memory B cells (CSMBs), natural killer (NK) T cells, and NK cell subpopulations were reduced in the adenoid tissues of children with both AH and AR (AH-AR) compared to AH-nAR children. Polysensitization in AH-AR children correlated with lower CSMB percentages. CONCLUSION: Polysensitivity to molds is associated with an increased risk of AH in children with AR. Fewer B cells, NK cells, and Treg cells with an effector/memory phenotype were detected in the adenoids of AR children, and these lower percentages of immune cells, particularly CSMBs, were closely linked to aeroallergen sensitization models and respiratory viral infection.

The value of the first postoperative diagnostic I-131 scan in patients with papillary thyroid carcinoma.

OBJECTIVE: To explore the feasibility of the postoperative diagnostic 131I whole-body planar scans (Dx-WBS) in papillary thyroid cancer (PTC) patients, and to clarify its value for accurate staging, risk stratification, and postoperative radioactive iodine (RAI) treatment management. DESIGN: Retrospective study from 2015 to 2021. SETTING: A total of 1294 PTC patients in the tertiary referral hospital. PARTICIPANTS: Patients with differentiated thyroid cancer who underwent total/subtotal thyroidectomy were included. Patients with non-PTC pathological type, non-first RAI treatment, and incomplete data such as Dx-WBS and postablation WBS (Rx-WBS) were excluded. METHODS: The diagnostic efficacy of Dx-WBS was calculated with Rx-WBS as the reference. All patients were initially staged by the 8th edition of TNM staging, and risk stratification was performed based on clinical and pathological information. After Dx-WBS, the risk stratification was re-evaluated, and management was reconfirmed. RESULTS: The detection rates of Dx-WBS for residual thyroid, cervical lymph nodes, upper mediastinal lymph nodes, lung, and bone distant metastasis were 97.6%, 78.3%, 82.1%, 66.7%, and 61.2%, respectively. The risk stratification of 113 patients (8.7%) changed after Dx-WBS, of which 107 patients changed from low to intermediate risk, 2 from low to high risk, and 4 from medium to high risk. A total of 241 patients (18.6%) adjusted the RAI regimen after Dx-WBS. CONCLUSION: This study confirms the diagnostic efficacy of the postoperative Dx-WBS in PTC patients and the value of Dx-WBS in accurately assessing risk stratification, as well as assisting in determining RAI treatment.

Contextualizing the revised Patient Perception of Patient-Centeredness (PPPC-R) scale in primary healthcare settings: a validity and reliability evaluation study.

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. SETTING/PARTICIPANTS: In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. RESULTS: The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: [Formula: see text], P < 0.001, RMSEA = 0.044, CFI = 0.981; factor loadings: 0.553 to 0.888). Cronbach's α also indicated good internal consistency reliability: The overall Cronbach's α was 0.922, and the Cronbach's α for each factor was 0.851, 0.872, and 0.717, respectively. CONCLUSIONS: The Chinese version of the PPPC scale provides a valuable tool for evaluating patient-centered medical service quality.

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.

Quality in screening and measuring blood pressure in China's primary health care: a national cross-sectional study using unannounced standardized patients.

Background: This study aims to evaluate primary care providers' adherence to the standard of measuring blood pressure for people aged 35 or above during their initial visit, as per Chinese guidelines, and to identify factors affecting their practices. Methods: We developed 11 standardized patients (SP) cases as tracer conditions to evaluate primary care, and deployed trained SPs for unannounced visits to randomly selected providers in seven provinces of China. The SPs used a checklist based on guidelines to record whether and how blood pressure was measured. Data were analyzed descriptively and regression analysis was performed to examine the association between outcomes and factors such as provider, patient, facility, and clinical case characteristics. Findings: The SPs conducted 1201 visits and found that less than one-third of USPs ≥35 had their blood pressure measured. Only 26.9% of migraine and 15.4% of diabetes cases received blood pressure measurements. Additionally, these measurements did not follow the proper guidelines and recommended steps. On average, 55.6% of the steps were followed with few providers considering influencing factors before measurement and only 6.0% of patients received both-arm measurements. The use of wrist sphygmomanometers was associated with poor blood pressure measurement. Interpretation: In China, primary care hypertension screening practices fall short of guidelines, with infrequent initiation of blood pressure measurements and inadequate adherence to proper measurement steps. To address this, priority should be placed on adopting, implementing, and upholding guidelines for hypertension screening and measurement. Funding: National Natural Science Foundation of China, Swiss Agency for Development and Cooperation, Doctoral Fund Project of Inner Mongolia Medical University, China Postdoctoral Science Foundation.

Job preferences of Chinese primary health care workers: A discrete choice experiment.

OBJECTIVE: Primary health workers (PHWs) are a critical pillar of health systems but primary health care centers often struggle to attract and retain talented staff. To better understand why this is, we investigated the job preference of PHWs in a Chinese urban setting. METHODS: In a discrete choice experiment, PHWs from 15 primary health care centers in Guangzhou, China, made trade-offs between several hypothetical job scenario combinations of salary, type of health institution, bianzhi (permanent post), work years required for promotion, career development and training opportunities, educational opportunities for children, and community respect. Based on the estimate of the mixed logit model, willingness to pay and policy simulations were applied to estimate the utility of each attribute. RESULTS: Data were collected from 446 PHWs. The PHWs were willing to forgo Chinese Renminbi 2806.1 (US$ 438.5) per month to obtain better education opportunities for their children, making it the most important non-monetary factor. Their preferences were also influenced relatively more by salary, bianzhi, and community respect, than with the other attributes we tested for, work years required for promotion, career development and training opportunities, and type of health institution. CONCLUSION: Salary is a robust predictive factor, while three non-monetary factors (opportunities for children's education, bianzhi, and community respect) are essential in retaining health workers in primary care.

A network pharmacology- and transcriptomics-based investigation reveals an inhibitory role of ß-sitosterol in glioma via the EGFR/MAPK signaling pathway.

Glioma is characterized by rapid cell proliferation, aggressive invasion, altered apoptosis and a poor prognosis. ß-Sitosterol, a kind of phytosterol, has been shown to possess anticancer activities. Our current study aims to investigate the effects of ß-sitosterol on gliomas and reveal the underlying mechanisms. Our results show that ß-sitosterol effectively inhibits the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, ß-sitosterol inhibits migration by downregulating markers of epithelial-mesenchymal transition (EMT). Mechanistically, network pharmacology and transcriptomics approaches illustrate that the EGFR/MAPK signaling pathway may be responsible for the inhibitory effect of ß-sitosterol on glioma. Afterward, the results show that ß-sitosterol effectively suppresses the EGFR/MAPK signaling pathway. Moreover, ß-sitosterol significantly inhibits tumor growth in a U87 xenograft nude mouse model. ß-Sitosterol inhibits U87 cell proliferation and migration and induces apoptosis and cell cycle arrest in U87 cells by blocking the EGFR/MAPK signaling pathway. These results suggest that ß-sitosterol may be a promising therapeutic agent for the treatment of glioma.

Super-resolution lensless imaging system based on a fast anti-diffraction algorithm.

Conventional lens imaging systems modulate incident rays with a set of lenses and focus these rays on their imaging planes. A lensless imaging system uses a single mask instead of lenses to project incident rays onto the imaging plane. These rays pass through or are blocked off according to the binary mask pattern. These systems are thin, lightweight, and inexpensive. However, they do not converge the rays, causing the local images corresponding to individual light transmission units to heavily overlap in a global scene, requiring a specific algorithm for decoding. Additionally, diffraction is unavoidable when the holes on the mask are extremely small, which can degrade the imaging quality. To address these difficulties, we propose a decoding algorithm called Fourier-ADMM algorithm to unwrap the overlapped images rapidly. In addition to providing high decoding speed, the proposed technique can suppress the diffraction from the tiny holes, owing to its conjugated structure. Based on this novel decoding algorithm, a lensless imaging system is proposed, which can handle overlapped and diffracted images with a single random mask. The camera can work beyond the theoretical diffraction limit and tremendously enhance the resolution. In summary, the super-resolution lensless camera provides users with additional options to suit different situations. It can facilitate robust, high-resolution, fast decoding without sophisticated calibration.

Circ_0020014 mediates CTSB expression and participates in IL-1ß-prompted chondrocyte injury via interacting with miR-24-3p.

BACKGROUND: Recent studies have shown that circRNAs are involved in the pathogenesis of osteoarthritis (OA) by affecting various fundamental cellular characteristics of chondrocytes. The purpose of this paper is to investigate the role and regulatory mechanism of hsa_circ_0020014 (circ_0020014) in chondrocytes of OA. METHODS: The inflammatory cytokine interleukin 1 beta (IL-1ß) was used to stimulate human chondrocytes. Cell viability, proliferation, and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Several protein levels were determined by western blotting (WB). Levels of inflammatory cytokines and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). Relative expression of circ_0020014 was estimated by real-time polymerase quantitative chain reaction (RT-qPCR). Bioinformatics prediction combined with dual-luciferase reporter, RIP and RNA pull-down assays were done to probe into the regulatory mechanism of circ_0020014. RESULTS: Circ_0020014 was overexpressed in OA patient-derived articular cartilages and IL-1ß-stimulated chondrocytes. Silencing of circ_0020014 lighted IL-1ß-prompted chondrocyte proliferation repression, apoptosis, inflammation, and oxidative stress. Mechanically, circ_0020014 functioned as a miR-24-3p molecular sponge to regulate cathepsin B (CTSB) expression. Furthermore, miR-24-3p inhibition alleviated circ_0020014 knockdown-mediation repression of IL-1ß-urged chondrocyte injury. In addition, CTSB overexpression whittled miR-24-3p upregulation-mediated suppression of IL-1ß-urged chondrocyte injury. CONCLUSION: Our findings demonstrated that the circ_0020014/miR-24-3p/CTSB axis was associated with IL-1ß-prompted chondrocyte injury, supporting the involvement of circ_0020014 in the OA pathogenesis.

Materials Design and System Innovation for Direct and Indirect Seawater Electrolysis.

Green hydrogen production from renewably powered water electrolysis is considered as an ideal approach to decarbonizing the energy and industry sectors. Given the high-cost supply of ultra-high-purity water, as well as the mismatched distribution of water sources and renewable energies, combining seawater electrolysis with coastal solar/offshore wind power is attracting increasing interest for large-scale green hydrogen production. However, various impurities in seawater lead to corrosive and toxic halides, hydroxide precipitation, and physical blocking, which will significantly degrade catalysts, electrodes, and membranes, thus shortening the stable service life of electrolyzers. To accelerate the development of seawater electrolysis, it is crucial to widen the working potential gap between oxygen evolution and chlorine evolution reactions and develop flexible and highly efficient seawater purification technologies. In this review, we comprehensively discuss present challenges, research efforts, and design principles for direct/indirect seawater electrolysis from the aspects of materials engineering and system innovation. Further opportunities in developing efficient and stable catalysts, advanced membranes, and integrated electrolyzers are highlighted for green hydrogen production from both seawater and low-grade water sources.

The Inferior Grain Filling Initiation Promotes the Source Strength of Rice Leaves.

Poor grain-filling initiation in inferior spikelets severely impedes rice yield improvement, while photo-assimilates from source leaves can greatly stimulate the initiation of inferior grain-filling (sink). To investigate the underlying mechanism of source-sink interaction, a two-year field experiment was conducted in 2019 and 2020 using two large-panicle rice cultivars (CJ03 and W1844). The treatments included intact panicles and partial spikelet removal. These two cultivars showed no significant difference in the number of spikelets per panicle. However, after removing spikelet, W1844 showed higher promotion on 1000-grain weight and seed-setting rate than CJ03, particularly for inferior spikelets. The reason was that the better sink activity of W1844 led to a more effective initiation of inferior grain-filling compared to CJ03. The inferior grain weight of CJ03 and W1844 did not show a significant increase until 8 days poster anthesis (DPA), which follows a similar pattern to the accumulation of photo-assimilates in leaves. After removing spikelets, the source leaves of W1844 exhibited lower photosynthetic inhibition compared to CJ03, as well as stronger metabolism and transport of photo-assimilates. Although T6P levels remained constant in both cultivars under same conditions, the source leaves of W1844 showed notable downregulation of SnRK1 activity and upregulation of phytohormones (such as abscisic acid, cytokinins, and auxin) after removing spikelets. Hence, the high sink strength of inferior spikelets plays a role in triggering the enhancement of source strength in rice leaves, thereby fulfilling grain-filling initiation demands.

Rectangular Amplitude Mask-Based Auto-Focus Method with a Large Range and High Precision for a Micro-LED Wafer Defects Detection System.

Auto-focus technology plays an important role in the Micro-LED wafer defects detection system. How to accurately measure the defocus amount and the defocus direction of the Micro-LED wafer sample in a large linear range is one of the keys to realizing wafer defects detection. In this paper, a large range and high-precision auto-focus method based on a rectangular amplitude mask is proposed. A rectangular amplitude mask without a long edge is used to modulate the shape of the incident laser beams so that the spot shape distribution of the reflected laser beam on the sensor changes with the defocus amount of the wafer sample. By calculating the shape of the light spots, the defocus amount and the defocus direction can be obtained at the same time. The experimental results show that under the 20× microscopy objective, the linear range of the auto-focus system is 480 µm and the accuracy can reach 1 µm. It can be seen that the automatic focusing method proposed in this paper has the advantages of large linear range, high accuracy, and compact structure, which can meet the requirements of the Micro-LED wafer defects detection equipment.

Exploring causal mechanisms and essential factors in the prevention and control of chlamydia in Guangdong, Southern China: a study protocol.

BACKGROUND: Chlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China. METHODS: Our study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions. DISCUSSION: Our study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior.

Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.

BACKGROUND: Current evidence shows that human induced pluripotent stem cells (hiPSCs) can effectively differentiate into keratinocytes (KCs), but its effect on skin burn healing has not been reported. AIM: To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms. METHODS: An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926, and GSE27186 was established. A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs. The expression of KCs marker proteins was detected using immunofluorescence staining. A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created, and then phosphate buffered saline (PBS), hiPSCs-KCs, or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface. The wound healing, re-epithelialization, engraftment of hiPSCs-KCs into wounds, proinflammatory factor level, and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining, carboxifluorescein diacetate succinimidyl ester (CFSE) fluorescence staining, enzyme linked immunosorbent assay, and Western blotting on days 3, 7, and 14 after the injection, respectively. Moreover, the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry, EdU, Transwell, and damage repair assays. RESULTS: HiPSCs-KCs could express the hallmark proteins of KCs. COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs. Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area, an increase in wound re-epithelialization, a decrease in proinflammatory factors content, and an inhibition of NF-κB pathway activation compared to the PBS group. The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration, providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration. CONCLUSION: In deep, second-degree burn wounds, COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

Dual-ring parity-time symmetric brillouin fiber laser with an unbalanced polarization Mach-Zehnder interferometer.

A dual-ring parity-time (PT) symmetric Brillouin fiber laser (BFL) with an unbalanced polarization Mach-Zehnder interferometer (UP-MZI) is proposed and experimentally investigated. An UP-MZI consisting of optical coupler, polarization beam combiner (PBC) and two asymmetric length arms with 10 km and 100 m single-mode fiber, is used to achieve Vernier effect and PT symmetry. Due to the orthogonally polarized lights created in the PBC, the dual-ring PT symmetry BFL with an UP-MZI implements two unbalanced length feedback rings that are connected to one another, one long length ring with a Brillouin gain and the other short length ring with a loss of the same magnitude, to break a PT symmetric and maintain the Vernier effect. By contrast with existing PT symmetry BFL studies, this design does not require same lengths of the gain and loss loops, but can manipulate freely PT symmetry status in accordance with a rational scaling factor between them. Experimental results reveal that the 3-dB linewidth of dual-ring PT symmetry BFL with an UP-MZI is about 4.85 Hz with the threshold input power of 9.5 mW, in accordance with the 97 Hz measured linewidth at the -20 dB power point. Within 60 mins of the stability experiment, the power and frequency stability fluctuation are ±0.02 dB and ±0.137 kHz, respectively. Thanks to the two asymmetric ring lengths, the sidemode suppression ratio (SMSR) is optimized by 54 dB compared to that with the only long ring structure, 26 dB when using only the Vernier effect or 12 dB for existing PT symmetry BFL. This BFL design with single longitudinal mode and high SMSR output can be applied to high coherent communication and Brillouin-based microwave photonics systems with low phase noise.

Ultra-Narrow Bandwidth Microwave Photonic Filter Implemented by Single Longitudinal Mode Parity Time Symmetry Brillouin Fiber Laser.

In this paper, a novel microwave photonic filter (MPF) based on a single longitudinal mode Brillouin laser achieved by parity time (PT) symmetry mode selection is proposed, and its unparalleled ultra-narrow bandwidth as low as to sub-kHz together with simple and agile tuning performance is experimentally verified. The Brillouin fiber laser ring resonator is cascaded with a PT symmetric system to achieve this MPF. Wherein, the Brillouin laser resonator is excited by a 5 km single mode fiber to generate Brillouin gain, and the PT symmetric system is configured with Polarization Beam Splitter (PBS) and polarization controller (PC) to achieve PT symmetry. Thanks to the significant enhancement of the gain difference between the main mode and the edge mode when the polarization state PT symmetry system breaks, a single mode oscillating Brillouin laser is generated. Through the selective amplification of sideband modulated signals by ultra-narrow linewidth Brillouin single mode laser gain, the MPF with ultra-narrow single passband performance is obtained. By simply tuning the central wavelength of the stimulated Brillouin scattering (SBS) pumped laser to adjust the Brillouin oscillation frequency, the gain position of the Brillouin laser can be shifted, thereby achieving flexible tunability. The experimental results indicate that the MPF proposed in this paper achieves a single pass band narrow to 72 Hz and the side mode rejection ratio of more than 18 dB, with a center frequency tuning range of 0-20 GHz in the testing range of vector network analysis, which means that the MPF possesses ultra high spectral resolution and enormous potential application value in the domain of ultra fine microwave spectrum filtering such as radar imaging and electronic countermeasures.

Quality-of-life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia.

BACKGROUND: Treatment-free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality-of-life (QoL) and mental health in CML patients with full-dose TKI, low-dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation. METHODS: We conducted a cross-sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation. RESULTS: 1450 responses were included in the analysis. 44.3% of respondents reported a moderate-to-severe impact of TKI treatment on their QoL. 17% of respondents had moderate-to-severe anxiety. 24.4% of respondents had moderate-to-severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long-term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full-dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping. CONCLUSIONS: TKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full-dose treatment to discontinuation. Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality-of-life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full-dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.