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Abstract The distributed power (DP) trading market plays a pivotal role in promoting renewable energy and driving the global economy’s low-carbon transition. However, the DP market worldwide is still in its infancy and faces problems such as immature market mechanisms and fluctuating power generation. To address these challenges, this paper introduces an innovative Hybrid Transaction Model (HTM) designed to optimize DP market mechanisms and refine “grid fee” structures. HTM operates through two structured transaction markets: (1) the aggregation transaction market, which manages trades between aggregators and distributed users; (2) the terminal transaction market, which facilitates exchanges between aggregators and industrial and commercial users. Additionally, HTM integrates a shared energy storage market to support expanding energy storage systems. Using China as a case study, this paper examines the barriers to DP trade market development and offers actionable policy implications for the further development of DP markets in China and comparable regions.

Abstract Background Dental filling is a prevalent method for treating dental defects. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward dental defects and dental fillings among dental patients in Jinan, Shandong Province, China. Methods This cross-sectional study was conducted at the main campus and several branch campuses of Jinan Stomatological Hospital, and community locations within Jinan city between October 2023, and January 2024. Spearman correlation analysis and mediation analysis were used to assess the associations and interrelationships between KAP scores. Results In this study, 2529 dental patients participated, with 69.1% being females. Of these, 1711 had no dental defects, 551 had defects and fillings, and 267 had defects without fillings. Their median knowledge, attitude, and practice (Questions 1–6) scores were 8.00 [5.00, 12.00] (possible range: 0–18), 27.00 [26.00, 29.00] (possible range: 10–50), and 19.00 [15.00, 24.00] (possible range: 9–45), respectively. Mediation analysis revealed that in patients without dental defects, knowledge had a direct effect on attitude (β = -0.983, 95% CI: -0.999, -0.966, P

Abstract Background Despite being preventable and curable, leprosy remains endemic in some undeveloped regions, including China. Wenshan Zhuang and Miao Autonomous Prefecture (Wenshan prefecture) currently bears the highest leprosy burden in China. In this ecological study, we aimed to analyze the epidemiological characteristics as well as identify and visualize the high-risk townships of Wenshan prefecture using the most updated leprosy data from 2010 to 2022. Methods Geographical information system combined with spatial scan statistics was used for newly detected leprosy cases abstracted from the Leprosy Management Information System in China. Global Moran’s I index was used to uncover the spatial pattern of leprosy at the township level. Spatial scan statistics, encompassing purely temporal, purely spatial, spatial variation in temporal trends, and space-time analysis, were implemented for detecting the risk clusters. Results Between 2010 and 2022, Wenshan prefecture detected 532 new leprosy cases, comprising 352 (66.17%) males and 180 (33.83%) females. The aggregated time primarily occurred between October 2010 and March 2014. The distribution pattern of newly detected leprosy cases was spatially clustered. We identified four high-risk spatial clusters encompassing 54.51% of the new cases. Furthermore, spatial variation in temporal trends highlighted one cluster as a potential high-risk area. Finally, two space-time clusters were detected, and the most likely cluster was predominantly located in the central and northwest regions of Wenshan prefecture, spanning from January 2010 to September 2013. Conclusions In this ecology study, we characterized the epidemiological features and temporal and spatial patterns of leprosy in Wenshan prefecture using the most recent leprosy data between 2010 and 2022. Our findings offer scientific insights into the epidemiological profiles and spatiotemporal dynamics of leprosy in Wenshan prefecture. Clinicians and policymakers should pay particular attention to the identified clusters for the prevention and control of leprosy.

Abstract The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient’s lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material.

Abstract Background Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. Methods This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. Results A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: −14.0 to − 10.5; P

Abstract In recent years, the emergence of the squeezed branch pile has presented a new avenue for civil engineering, offering a distinctive structure and favorable mechanical characteristics. Squeezed branch piles have strong compressive, uplift, and horizontal load resistance capabilities. Due to the existence of discs, the geometric parameters of squeezed branch piles are abundant but important. This article selects number of discs, disc diameter, disc squeeze angle, and disc spacing as the main influencing factors on the bearing capacity of squeezed branch piles and conducts a qualitative analysis of their mechanical properties. The aim of this article is to analyze the different bearing performances of squeezed branch piles through orthogonal experimental design, simulate test conditions using finite element software ABAQUS, obtain relevant data, and finally determine the weight ranking and optimal combination of influencing factors through range analysis to provide better guidance for engineering practices. Through multi-objective optimization design, six optimization objectives including compressive performance, compressive economic efficiency, uplift performance, uplift economic efficiency, maximum horizontal displacement and maximum bending moment of pile body were analyzed. The analysis methods used included comprehensive balance method, queue scoring method, principal component analysis method, entropy weight method, and analytic hierarchy process. The conclusions obtained are similar, and based on the judgment, the squeezed branch pile with 4 discs, disc diameter of 2.5D, disc squeeze angle of 35°, and disc spacing of 3D is considered as the optimal combination under consideration of all optimization objectives.

ObjectivesThe present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China.MethodsA total of 219 new leprosy cases during two periods, 2018–2019 and 2020–2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods.ResultsThere was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January–March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K.ConclusionCOVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

ObjectiveThis study aims to develop and validate the Posttraumatic Cognitive Appraisal Inventory (PTCAI) for accidental trauma survivors.MethodBased on interviews and expert feedback, the initial item pool was generated for the Negative Cognitive Appraisal Inventory of Loss and Feeling Threatened, and the Positive Cognitive Appraisal Inventory of Positively Face, Self-Sense, and Relationships. Then, we recruited two groups of accidental trauma survivors to examine the reliability and validity of the PTCAI. Item analysis and exploratory factor analysis (EFA) were conducted on Sample 1. Confirmatory factor analysis (CFA), Pearson correlation analysis, and internal consistency reliability analysis were applied to Sample 2. After 2 weeks, 20 survivors completed the PTCAI again to test temporal stability.ResultsFollowing item analysis, the PTCAI was reduced to 27 items. The results of the EFA demonstrated that the five-factor, 27-item solution of the PTCAI was appropriate, which accounted for 63.931% of the total variation. The CFA indicated that the five-factor second-order model offered an excellent fit to the data. Loss and Feeling threatened were equally important in the study participants’ negative cognitive appraisal of accidental traumas. Self-sence was the most important positive cognitive appraisal of accidental traumas by the study participants. Positively Face and Relationships were somewhat behind. Additionally, the PTCAI demonstrated high concurrent validity and reliability (test–retest and internal consistency).ConclusionThe PTCAI appears to be a reliable and valid instrument for assessing cognitive appraisals of accidental trauma survivors.

AbstractBackground Radiofrequency ablation (RFA) is a first-line treatment for early-stage hepatocellular carcinoma (HCC). However, the recurrence after RFA remains an urgent challenge. Current studies have shown that residual tumor after RFA is an important cause of recurrence.Objective We hypothesized that the products of dead tumor cells after RFA have direct effects on the development of residual tumors. Further, we investigated the underlying mechanisms.Methods The proliferation and invasion ability of HepG2 and Huh7 cells were assessed using CCK-8, colony formation, EdU, transwell invasion and migration assay. Immunofluorescence and western blotting were used to show HMGB1 released from dead tumor cells. The levels of MMP2, MMP9, CyclinE1 and pERK1/2 were determined using western blotting. Finally, in vivo validation was performed in BALB/c nude mice xenograft tumor models.Results The products of dead tumor cells after thermal treatment can promote the proliferation and invasion of residual HCC cells. Dead tumor cells could release high-mobility group box 1 (HMGB1) after thermal treatment. Similar to the products of dead tumor cells, the recombinant protein of HMGB1 can promote the proliferation and invasion of residual HCC cells. Moreover, HMGB1 could bind to receptor of advanced glycation end-products. Then, it activated the ERK1/2 pathway and significantly upregulated the expressions of MMP2, MMP9, and CyclinE1.Conclusion Our study reveals that HMGB1 released by dead tumor cells after thermal treatment can promote the proliferation and invasion of residual HCC cells. Hence, the HMGB1/RAGE/ERK1/2 pathway is a potential target for improving the prognosis of HCC after radiofrequency ablation.

Abstract γδ‐T cells are innate‐like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ‐T cells (γδ‐T‐EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether γδ‐T‐EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that γδ‐T‐EVs had immune adjuvant effects on antigen‐presenting cells, as revealed by enhanced expression of antigen‐presenting and co‐stimulatory molecules, secretion of pro‐inflammatory cytokines and antigen‐presenting ability of DCs after γδ‐T‐EVs treatment. The γδ‐T‐EVs‐based vaccine was designed by loading tumor‐associated antigens (TAAs) into γδ‐T‐EVs. Compared with γδ‐T‐EVs, the γδ‐T‐EVs‐based vaccine effectively promoted more tumor‐specific T‐cell responses. In addition, the vaccine regimen preserved direct antitumor effects and induced tumor cell apoptosis. Interestingly, the allogeneic γδ‐T‐EVs‐based vaccine showed comparable preventive and therapeutic antitumor effects to their autologous counterparts, indicating a better way of centralization and standardization in clinical practice. Furthermore, the allogeneic γδ‐T‐EVs‐based vaccine displayed advantages over the DC‐EVs‐based vaccine through their dual antitumor activities. This study provides a proof‐of‐concept for using the allogeneic γδ‐T‐EVs‐based vaccine in cancer control.

Objectives: As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a meta-analysis on the resistance of Mycobacterium leprae (M. leprae) to rifampicin and estimated drug resistance in different therapeutic states and regions. Methods: Embase, Medline, PubMed, and Web of Science were searched to identify studies between 1 January 1993 and 1 January 2022. Two independent reviewers extracted study data. Pooled cumulative incidences were computed using random-effects meta-analyses. Results: We included 32 papers describing the resistance of M. leprae to rifampicin (pooled cumulative incidences, 11% [95% confidence interval {CI}, 7% to 15%]). Therapeutic states and regional distribution were obtained for subgroup analyses. A total of 51 of 1135 new cases (pooled incidence, 10% [95% CI, 5% to 16%]) and 81 of 733 relapsed cases (pooled incidence, 20% [95% CI, 13% to 27%]) had rifampicin resistance. A total of 139 participants, including 11 patients with rifampicin resistance (pooled incidence, 42% [95% CI, −21% to 105%]), were nonresponsive and intractable cases. The incidence of rifampicin resistance was highest in the Western Pacific (pooled incidence, 21% [95% CI, 13% to 29%]) and lowest in the Americas (pooled incidence, 4% [95% CI, 1% to 7%]). Conclusions: Drug resistance testing and a robust and rigorous surveillance system are recommended to detect the prevalence of drug resistance in leprosy.

Abstract A conductive, elastic, and biocompatible hybrid network hydrogel was prepared by cross-linking of locust bean gum, polyvinyl alcohol, and carbon nanotubes, yielding a rough top surface and smooth bottom surface. The merging of the two pieces of hydrogel flat face to flat face forms a highly elastic hydrogel with double-rough surfaces. A piezoresistive sensor assembled with the double-rough surface hydrogel sandwiched between two carbon cloth electrodes exhibits a high sensitivity (20.5 kPa-1, 0-1kPa), a broad detection range (0.1–100 kPa) and a reliable response for 1000 cycles. The rough contact area between the hydrogels and the carbon cloth is found critical in achieving ultra-high sensitivities in the low-pressure range. Moreover, further monolithic integration of the sensor with a flexible solid-state zinc ion battery ensures the self-powering of the sensor for various human motions detection applications.

Abstract As a vital road construction machine, the bridge erecting machine works in a very complex environment. The brake as an important link to maintain the safety and stability of the bridge erecting machine, it will have serious consequences if it is failed. Establishing the brake simulation model and specifying the fault characteristics according to the actual operation status will make it more efficient to find the cause of faults and maintain the safety of machine for a long time. A simulation model of brake of the bridge erecting machine was established by Adams. The brake arms and center axis with obvious data characteristics were flexibly processed, and finite elements were analysed using Abaqus. To verify the accuracy of simulation models, rectangular rosettes were applied to special geometric points, and the strain data were gathered by using the DH3816N collector and compared with the simulation model. The Adams kinematic simulation model was used to simulate the actual operating conditions by the experiment of the disc springs. Two typical fault phenomena were selected: reduced insufficient of disc spring and oil pressure, and two fault characteristics were extracted: variation of the brake shoe clearance and variation of the braking system pressure. When the brake generates the fault characteristics, the normal operation of the brake will not be affected if the fault characteristics are in the first stage. When the fault characteristics are beyond the critical threshold, the faults phenomena of the brake are generated. The results of the simulation experiments proved that the method of using the simulation model to extract the fault characteristics of the braking system and distinguish the causes of the fault was feasible.

Biomimetic nanocomposites are widely used in the biomedical field because they can effectively solve the problems existing in the current cancer treatment by realizing multi-mode collaborative treatment. In this study, we designed and synthesized a multifunctional therapeutic platform (PB/PM/HRP/Apt) with unique working mechanism and good tumor treatment effect. Prussian blue nanoparticles (PBs) with good photothermal conversion efficiency were used as nuclei and coated with platelet membrane (PM). The ability of platelets (PLTs) to specifically target cancer cells and inflammatory sites can effectively enhance PB accumulation at tumor sites. The surface of the synthesized nanocomposites was modified with horseradish peroxidase (HRP) to enhance the deep penetration of the nanocomposites in cancer cells. In addition, PD-L1 aptamer and 4T1 cell aptamer AS1411 were modified on the nanocomposite to achieve immunotherapy and enhance targeting. The particle size, UV absorption spectrum and Zeta potential of the biomimetic nanocomposite were determined by transmission electron microscope (TEM), Ultraviolet-visible (UV-Vis) spectrophotometer and nano-particle size meter, and the successful preparation was proved. In addition, the biomimetic nanocomposites were proved to have good photothermal properties by infrared thermography. The cytotoxicity test showed that it had a good killing ability of cancer cells. Finally, thermal imaging, tumor volume detection, immune factor detection and Haematoxilin-Eosin (HE) staining of mice showed that the biomimetic nanocomposites had good anti-tumor effect and could trigger immune response in vivo. Therefore, this biomimetic nanoplatform as a promising therapeutic strategy provides new inspiration for the current diagnosis and treatment of cancer.

IntroductionTwo doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data.MethodsWith an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored.ResultsA homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified.DiscussionThe primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.

To estimate the physical dose of skin and key organs in a case of overexposure during a cardiac interventional procedure. Methods: The female patient aged 50 suffered from overexposure during cardiac interventional therapy in a hospital, Xinxiang city, Henan province, China in January 2020. The mesh-type phantom for the patient was constructed based on the adult mesh-type reference computational phantoms (MRCPs) released by the International Commission on Radiological Protection Publication 145 (ICRP145) and phantom deformation technology. Models of exposure scenario were constructed and simulated with particle and heavy ion transport code system (PHITS) according to exposure conditions. Results: The maximum absorbed dose of key organs/tissues under irradiation in posteroanterior (PA) and 30° left anterior oblique directions(LOA) was 632.4 and 305.6 ​mGy, respectively. The left lung, heart, and left mammary gland received a larger dose under both irradiation conditions. The ratio of the absorbed dose with and without shielding was calculated, and the relative difference in most organs was

Currently, there is a wealth of data and expert knowledge available on monitoring agro-meteorological disasters. However, there is still a lack of technical means to organically integrate and analyze heterogeneous data sources in a collaborative manner. This paper proposes a method for monitoring agro-meteorological disasters based on a spatio-temporal knowledge graph. It employs a semantic ontology framework to achieve the organic fusion of multi-source heterogeneous data, including remote sensing data, meteorological data, farmland data, crop information, etc. And it formalizes expert knowledge and computational models into knowledge inference rules, thereby enabling monitoring, early warning, and disaster analysis of agricultural crops within the observed area. The experimental area for this research is the wheat planting region in three counties in Henan Province. The method is tested using simulation monitoring, early warning, and impact calculation of the past two occurrences of dry hot wind disasters. The experimental results demonstrate that the proposed method can provide more specific and accurate warning information and post-disaster analysis results compared to raw records. The statistical results of NDVI decline also validate the correlation between the severity of wheat damage caused by dry hot winds and the intensity and duration of their occurrences. Regarding remote sensing data, this paper proposes a method that directly incorporates remote sensing data into spatio-temporal knowledge inference calculations. By integrating remote sensing data into the regular monitoring process, the advantages of remote sensing data granted by continuous observation are utilized. This approach represents a beneficial attempt to organically integrate remote sensing and meteorological data for monitoring, early warning, and evaluation analysis of agro-meteorological disasters.

Atypical disease presentations are common in older adults with COVID-19. The objective of this study was to determine the prevalence of atypical and typical symptoms in older adults with COVID-19 through progressive pandemic waves and the association of these symptoms with in-hospital mortality. This retrospective cohort study included consecutive adults aged over 65 years with confirmed COVID-19 infection who were admitted to seven hospitals in Toronto, Canada, from 1 March 2020 to 30 June 2021. The median age for the 1786 patients was 78.0 years and 847 (47.5%) were female. Atypical symptoms (as defined by geriatric syndromes) occurred in 1187 patients (66.5%), but rarely occurred in the absence of other symptoms (n = 106; 6.2%). The most common atypical symptoms were anorexia (n = 598; 33.5%), weakness (n = 519; 23.9%), and delirium (n = 449; 25.1%). Dyspnea (adjusted odds ratio [aOR] 2.05; 95% confidence interval [CI] 1.62–2.62), tachycardia (aOR 1.87; 95% CI 1.14–3.04), and delirium (aOR 1.52; 95% CI 1.18–1.96) were independently associated with in-hospital mortality. In a cohort of older adults hospitalized with COVID-19 infection, atypical presentations frequently overlapped with typical symptoms. Further research should be directed at understanding the cause and clinical significance of atypical presentations in older adults.

ObjectiveTo investigate the critical prognostic factors of patients with traumatic optic neuropathy (TON) treated with endoscopic transnasal optic canal decompression (ETOCD) and to perform multimodal analysis based on imaging examinations of optical coherence tomography angiography (OCTA) and CT scan. Subsequently, a new prediction model was established.MethodsThe clinical data of 76 patients with TON who underwent decompression surgery with the endoscope-navigation system in the Department of Ophthalmology, Shanghai Ninth People's Hospital from January 2018 to December 2021 were retrospectively analyzed. The clinical data included demographic characteristics, reasons for injury, interval between injury and surgery, multimode imaging information of CT scan and OCTA, including orbital fracture, optical canal fractures, vessel density of optic disc and macula, and the times of postoperative dressing change. Binary logistic regression was used to establish a model for best corrected visual acuity (BCVA) after treatment as a predictor of TON outcome.ResultsPostoperative BCVA improved in 60.5% (46/76) patients and did not improve in 39.5% (30/76) patients. The times of postoperative dressing change had a significant impact on the prognosis. Other factors affecting the prognosis were microvessel density of the central optic disc, the cause of injury, and the microvessel density above the macula. The area under the raw current curves of the predictive model was 0.7596.ConclusionsThe times of dressing changes after the operation, i.e., continuous treatment, is the key factor affecting prognosis. The microvessel density in the center of the optic disc and superior macula, quantitatively analyzed by OCTA, is the prognostic factor of TON and may be used as a prognostic marker of TON.

Abstract Sepsis is a potentially fatal condition caused by infection. It is frequently difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS), often resulting in poor prognoses and the misuse of antibiotics. Hence, highly sensitive and specific biomarkers are needed to differentiate sepsis from SIRS. Urine samples were collected and segregated by group (a sepsis group, a SIRS group, and a healthy control group). iTRAQ was used to identify the differentially expressed proteins among the three groups. The identified proteins were measured by ELISA in urine samples. Finally, all the acquired data were analyzed in SPSS. C-reactive protein, leucine-rich alpha glycoprotein-1 and serum amyloid A (SAA) protein were differentially expressed among the three groups. The adjusted median concentrations of urinary C-reactive protein were 1337.6, 358.7, and 2.4 in the sepsis, SIRS, and healthy control groups, respectively. The urinary leucine-rich alpha glycoprotein-1 levels in these three groups were 1614.4, 644.5, and 13.6, respectively, and the levels of SAA were 6.3, 2.9, and 0.07, respectively. For all three of these measures, the sepsis group had higher levels than the SIRS group (P

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

Batched Sparse (BATS) codes are a type of network coding scheme that use a combination of random linear network coding (RLNC) and fountain coding to enhance the reliability and efficiency of data transmission. In order to achieve unequal error protection for different data, researchers have proposed unequal error protection BATS (UEP-BATS) codes. However, current UEP-BATS codes suffer from high error floors in their decoding performance, which restricts their practical applications. To address this issue, we propose a novel UEP-BATS code scheme that employs a precoding stage prior to the weighted BATS code. The proposed precoding stage utilizes a partially regular low-density parity-check (PR-LDPC) code, which helps to mitigate the high error floors in the weighted BATS code We derive the asymptotic performance of the proposed scheme based on density evolution (DE). Additionally, we propose a searching algorithm to optimize precoding degree distribution within the complexity range of the precoding stage. Simulation results show that compared to the conventional weighted BATS codes, our proposed scheme offers superior UEP performance and lower error floor, which verifies the effectiveness of our scheme.

Graphical AbstractSS, short stature; SDS, standard deviation scores; Control, normal height, n=30; ISS, idiopathic short stature n=31; GHD, short stature caused by growth hormone deficiency, n=29.

The diagnosis of paucibacillary (PB) leprosy often possesses a diagnostic challenge, especially for pure neuritic and lesser skin lesions with the zero bacillary load, requiring a sensitive and accurate diagnostic tool. We have included 300 clinically diagnosed new leprosy cases (comprising 98 PB cases) and analyzed the sensitivity and specificity of PB leprosy cases by nested PCR with folP, gyrA, rpoB, RLEP, and 16SrRNA and Enzyme-linked Immunospot Assay test (ELISPOT) with MMPII, NDO-BSA, and LID-1 antigens by detecting interferon gamma (IFN-γ) release. The overall positivity rates of genes tested in 300 clinical specimens were identified as 55% of 16SrRNA, 59% of RLEP, 59.3% of folP, 57.3% of rpoB, 61% of gyrA while 90% of nested folP, 92.6% of nested rpoB, and 95% of nested gyrA, and 285 (95%) of at least one gene positive cases. For PB specimens, 95% PCR positivity was achieved by three tested genes in nested PCR. The data obtained from ELISPOT for three antigens were analyzed for IFN-γ expression with 600 subjects. Among 98 PB leprosy cases, the sensitivity of MMP II, LID-1, and NDO-BSA was 90%, 87%, and 83%, respectively, and the specificity was 90%, 91%, and 86%, respectively. The total number of cases positive for at least one antigen was 90 (91.8%) in PB, which is significantly higher than that in multibacillary (MB) leprosy (56.7%). The combination of multi-targets nested PCR and ELISPOT assay provides a specific tool to early clinical laboratory diagnosis of PB leprosy cases. The two assays are complementary to each other and beneficial for screening PB patients.

Abstract Residual tumors after insufficient radiofrequency ablation (IRFA) shows accelerated progression and anti‐PD‐1 resistance. It is also reported that macrophages infiltrating into residual tumors leads to anti‐PD‐1 resistance. Elements of autophagy have been detected to conjugate LC3 to be increasingly expressed in residual tumors. The underlying mechanisms between LC3 and macrophages are aimed to be investigated, and explore further ways to enhance immunotherapy in treating residual tumors. In mice models and patients, macrophages demonstrate increased infiltration into residual tumors, especially surrounding the ablated zone. Single‐cell transcriptome demonstrates enhancement of immunosuppression function in macrophages after IRFA. It is shown that macrophages engulf heat‐treated cells through LC3‐associated phagocytosis (LAP), enhance IL‐4 mediated macrophage programming through the PI3Kγ/AKT pathway, and suppress T cell proliferation. Blockade of the PI3Kγ/AKT pathway enhances the antitumor activity of PD‐1 blockades, inhibits malignant growth, and enhances survival in post‐IRFA models. In conclusion, in mice models and patients, macrophages demonstrate increased infiltration around ablated zones in residual tumors. Blockade of the PI3Kγ/AKT pathway suppresses the growth of residual tumors in subcutaneous and orthotopic models. The results illustrate the translational potential of PI3Kγ inhibitors to enhance anti‐PD‐1 therapy for the treatment of residual tumors after IRFA.

ATP acts as a co-substrate in enzyme catalysed reactions, but can also specifically bind metal ions. Here, the authors show that ATP interacts with copper ions and forms a Cu(II)-ATP complex that efficiently catalyses Diels-Alder reactions, and determine ATP residues that are essential for this activity.

Objectives: Understanding the nature of Mycobacterium leprae transmission is vital to implement better control strategies for leprosy elimination. The present study expands the knowledge of county-level strain diversity, distribution, and transmission patterns of leprosy in endemic provinces of China. Methods: We genetically characterized 290 clinical isolates of M. leprae from four endemic provinces using variable number tandem repeats (VNTR) and single nucleotide polymorphisms (SNPs). Attained genetic profiles and cluster consequences were contrasted with geographical and migration features of leprosy at county levels. Results: Considering the allelic variability of 17 VNTR loci by the discriminatory index, (GTA)9, (AT)17, (AT)15, (TA)18, (TTC)21, and (TA)10 are reported to be more highly polymorphic than other loci. The VNTR profile generated the low-density clustering pattern in the counties of Sichuan and Yunnan, whereas clusters have been observed from the isolates from Huayuan (N = 6), Yongding (N = 3), Zixing (N = 3), Chenxi (N = 2) and Zhongfang (N = 2) counties of Hunan, and Zhijin (N = 3), Anlong (N = 2), Zhenning (N = 2), and Xixiu (N = 2) counties of Guizhou. In some clusters, people’s social relations have been observed between villages. From the 290 clinical isolates, the most predominantly reported SNP was 3K (278, 95.8%), followed by SNP 1D (10, 3.4%), which are typically observed to be predominant in China. We also detected the novel SNP 3J (2, 0.8%), which has not yet been reported in China. Conclusion: The clustering pattern of M. leprae indicates the transmission of leprosy still persists at county levels, suggesting that there is a need to implement better approaches for tracing the close contacts of leprosy patients.

Introduction and objectives: Research in the last few years has proven that inhibition of fatty acid synthase (FASN) suppresses the migration and invasion of hepatoma carcinoma cells. This study aims to explore the effect of fatty acid synthase knockdown on the apoptosis and proliferation of HepG2 cells. Materials and methods: The human liver cancer cell line HepG2 was cultured and then transfected with FASN-specific siRNA and negative control RNAi. After 48 h, cells and protein lysates were used for western blotting, CCK-8 (cell counting kit-8) assays, flow cytometry and other tests. To assess cell apoptosis, Bax, Bcl-2 and caspase-3 were detected; to assess proliferation, CDK4 (cyclin-dependent kinases 4) and P21 were detected; and to determine the signaling pathway involved, β-catenin and C-myc were also detected. Results: Inhibition of FASN in HepG2 cells can decrease proliferation and promote apoptosis. Flow cytometry and CCK-8 assays demonstrated that the apoptosis rate of FASN-specific siRNA-transfected cells was significantly increased compared to that of the control cells (p

Abstract Background Fatty acid synthase (FASN) is highly expressed in various types of cancer and has an important role in carcinogenesis and metastasis. To clarify the mechanisms of FASN in liver cancer invasion and metastasis, the FASN protein interaction network in liver cancer was identified by targeted proteomic analysis. Methods Wound healing and Transwell assays was performed to observe the effect of FASN during migration and invasion in liver cancer. Isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry were used to identify proteins interacting with FASN in HepG2 cells. Differential expressed proteins were validated by co-immunoprecipitation, western blot analyses and confocal microscopy. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to demonstrate the mechanism of FASN regulating metastasis. Results FASN knockdown inhibited migration and invasion of HepG2 and SMMC7721 cells. A total of, 79 proteins interacting with FASN were identified. Additionally, gene ontology term enrichment analysis indicated that the majority of biological regulation and cellular processes that the FASN-interacting proteins were associated with. Co-precipitation and co-localization of FASN with fascin actin-bundling protein 1 (FSCN1), signal-induced proliferation-associated 1 (SIPA1), spectrin β, non-erythrocytic 1 (SPTBN1) and CD59 were evaluated. Knockdown of FASN in liver cancer reduced the expression of FSCN1, SIPA1, SPTBN1 and CD59. Furthermore, inhibition of FASN, FSCN1 or SPTBN1 expression in liver cancer resulted in alterations of epithelial–mesenchymal transition (EMT)-associated markers E-cadherin, N-cadherin, vimentin and transcription factors, Snail and Twist, at the mRNA level, and changes in matrix metallopeptidase (MMP)-2 and MMP-9 protein expression. Conclusion The results suggested that the FASN-interacting protein network produced by iTRAQ-based proteomic analyses may be involved in regulating invasion and metastasis in liver cancer by influencing EMT and the function of MMPs.

This study was designed to identify differently expressed circular RNAs (circRNAs) and investigate their potential roles in lacrimal sacs from patients with chronic dacryocystitis. The lacrimal sac samples of three chronic dacryocystitis patients and three control subjects were collected for RNA sequencing after ribosomal RNA was depleted. Differently expressed circRNAs and messenger RNAs (mRNAs) were used for co-expression analysis. CircRNA-microRNA (miRNA)-mRNA interaction network were also established by miRanda software. Meanwhile, pathway and functional enrichment analysis were conducted for the down- and up-regulated mRNAs in the circRNA-mRNA co-expression network. The expression levels of circRNAs and mRNAs in chronic dacryocystitis and control samples were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). In all the 3,909 circRNAs predicted through RNA sequencing, 25 circRNAs (20 up-regulated and 5 down-regulated) expressed differently in chronic dacryocystitis samples. Besides, there identified 1,486 differentially expressed mRNAs. Of these differently expressed circRNAs and mRNAs, eight were validated by qRT-PCR, including MYH2, DSP, CD27, CCL5, FN1, has_circ_0004792, has_circ_0001062, and has_circ_0115476. Gene Ontology (GO) analysis indicated that the majority of altered mRNAs in this co-expression network were involved in immune system processes and meanwhile Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these altered expressed mRNAs were also amplified in bacterial invasion of epithelial cells, both of which were thought to be involved in the pathogenesis of chronic dacryocystitis. In the circRNA-miRNA-mRNA interaction network, six circRNAs were found to be related to Th1 and Th2 cell differentiation, which was closely associated with the development of chronic dacryocystitis. This study identified statistically significant differences between circRNAs and mRNAs of lacrimal sac samples of chronic dacryocystitis patients and control individuals and provides novel insight into the regulatory mechanism of circRNAs, miRNAs, and mRNAs in the pathogenesis of chronic dacryocystitis.

Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.

Introduction: A reliable biomarker is urgently needed in the diagnosis and management of acid sphingomyelinase deficiency (ASMD, also known as Niemann Pick A, A/B, and B). Lyso-sphingomyelin (LSM) has previously been proposed as a biomarker for this disease. However, existing studies have not investigated the relationship between LSM levels and clinical subtype or severity. The purpose of this study is to address this gap in knowledge. Material and methods: We present a cross-sectional study of 28 patients with ASMD, enrolled in an ongoing natural history study at the Icahn School of Medicine at Mount Sinai and The Children's Hospital at Montefiore. Plasma LSM levels from 28 patients were analyzed, including 7 patients with the infantile neurovisceral phenotype (ASMD type A), 3 patients with chronic neurovisceral disease (ASMD type A/B) and 18 patients with chronic visceral ASMD (ASMD type B). The association between LSM levels and clinical subtype, dichotomized as infantile (type A) or chronic (type A/B and B), was analyzed using the Wilcoxon rank sum test. In secondary analysis, the association between LSM levels and clinical severity among the chronic ASMD patients was analyzed using the Kruskal-Wallis test. Results: LSM levels were elevated in all patients with ASMD when compared to a reference range of (0.04–3.8 (ng/mL)). Median LSM levels were higher in patients with infantile ASMD (386 ng/mL [314, 605]) compared to chronic ASMD (133 ng/mL [90, 209]), p

Objective Overview on risks of acupuncture-related adverse events (AEs).Design Systematic review and meta-analyses of prospective studies.Data sources PubMed, Scopus and Embase from inception date to 15 September 2019.Eligibility criteria for selecting studies Prospective studies assessing AEs caused by needle acupuncture in humans as primary outcome published in English or German.Data extraction and synthesis Two independent researchers selected articles, extracted the data and assessed study quality. Overall risks and risks for different AE categories were obtained from random effects meta-analyses.Main outcomes Overall risk of minor AEs and serious adverse events (SAEs) per patients and per treatments.Results A total of 7679 publications were identified. Twenty-two articles reporting on 21 studies were included. Meta-analyses suggest at least one AE occurring in 9.31% (95% CI 5.10% to 14.62%, 11 studies) of patients undergoing an acupuncture series and in 7.57% (95% CI 1.43% to 17.95%, 5 studies) of treatments. Summary risk estimates for SAEs were 1.01 (95% CI 0.23 to 2.33, 11 studies) per 10 000 patients and 7.98 (95% CI 1.39 to 20.00, 14 studies) per one million treatments, for AEs requiring treatment 1.14 (95% CI 0.00 to 7.37, 8 studies) per 1000 patients. Heterogeneity was substantial (I2 >80%). On average, 9.4 AEs occurred in 100 treatments. Half of the AEs were bleeding, pain or flare at the needle site that are argued to represent intended acupuncture reaction. AE definitions and assessments varied largely.Conclusion Acupuncture can be considered among the safer treatments in medicine. SAEs are rare, and the most common minor AEs are very mild. AEs requiring medical management are uncommon but necessitate medical competence to assure patient safety. Clinical and methodological heterogeneity call for standardised AE assessments tools, clear criteria for differentiating acupuncture-related AEs from therapeutically desired reactions, and identification of patient-related risk factors for AEs.PROSPERO registration number CRD42020151930.

Subway concrete is easy to be attacked by carbonation in the relatively closed space, and alkali silica reaction (ASR) is a serious durability problem of concrete, which is difficult to find and repair. The damage caused by carbonation and ASR seriously affects the durability of subway concrete. Two kinds of nano-particles (nano-SiO2 and nano-Fe2O3) are mixed into plain subway concrete in this paper, and their effects on the durability of concrete under the combined action of carbonation and ASR are studied experimentally. The test results show that, after mixing with nano-particles, the carbonation depth and expansion of subway concrete are decreased, as well as the sonic velocity of subway concrete is increased obviously, which demonstrate the durability of subway concrete with nano-particles is better than plain subway concrete. The enhancement of durability is due to the special physical and chemical properties of nanoparticles, which can improve the microstructure of concrete and the chemical composition of pore solution in concrete.

To identify the microorganism distribution clinical characteristics and management of cutaneous Mycobacterium tuberculosis and nontuberculous mycobacterial infectious diseases in the past 10 years we collected and analyzed the patient records of all cutaneous M. tuberculosis and nontuberculous mycobacterial infection cases diagnosed by culture and/or PCR from 2008 to 2017 in the Hospital of Dermatology Chinese Academy of Medical Sciences. Among 203 cases including 89 M. tuberculosis infections and 114 nontuberculous mycobacterial infections M. tuberculosis was the most common species in all patients and M. marinum predominated among the nontuberculous mycobacterial followed by M. abscessus. Cases of cutaneous mycobacterial infection especially nontuberculous mycobacterial infection increased in the past 10 years and infection with rapidly growing mycobacteria significantly increased in the last 5 years in this national hospital in Southeast China. Injuries were common causative factors. Approximately 91.3% of patients responded well to longstanding antibiotic therapy.

Whether Mycobacterium leprae transmits from placenta to fetus remains unknown. We describe the case of a pregnant woman with untreated histoid leproma. Although her newborn was healthy, laboratory examination revealed intact M. leprae present in the placenta, suggesting that the placental barrier might prevent vertical dissemination of M. leprae.

ABSTRACTReports on antimicrobial resistance (AMR) of Mycobacterium leprae, relationship with bacteriological index (BI), and transmission in China are limited. We investigated the emergence of AMR mutations, the relationship between BI and AMR in complete, moderate and lack of BI decline cases, and molecular epidemiological features of AMR cases by enrolling 290 leprosy cases from four endemic provinces. Seven (2.41%), one (0.34%), five (1.72%), one (0.34%), and one (0.34%) strains had single mutations in folP1, rpoC, gyrA, gyrB, and 23S rRNA, respectively. Double mutations in folP1 and gyrA, rpoB and gyrA, and gyrA and 23S rRNA were observed in one (0.34%) strain each. Mutated strains occurred in three out of 81 (95% CI−0.005-0.079, p = 0.083) cases with complete BI decline, in seven out of 103 (95% CI 0.018-0.117, p = 0.008) cases with moderate BI decline, and in four out of 34 (95% CI 0.003-0.231, p = 0.044) cases with lack of BI decline. Most of these mutated strains were geographically separated and diverged genotypically. AMR mutations may not be the main cause of the lack of BI decline. The low transmission of AMR strains at the county level indicates an ongoing transmission at close contact levels.

Alkali-silica reaction (ASR) is a serious durability problem, resulting in significant maintenance and reconstruction cost of concrete infrastructure all over the world, so more and more attention has been attracted to it. This paper tends to discuss whether nano-SiO2 and nano-Fe2O3 can mitigate the concrete deterioration caused by ASR. The test results show that the concretes with nano-particles have lower expansion and higher sonic velocity. Therefore, it is an available method for concrete to mix with nano-particles to mitigate ASR and the optimum content of nano-SiO2 and nano-Fe2O3 in concrete is 2.0% and 1.0%, respectively. The mitigating mechanism is revealed through the effect of mixing water on the porosity.