Comparison of Thoracoscopy-Guided Thoracic Paravertebral Block and Ultrasound-Guided Thoracic Paravertebral Block in Postoperative Analgesia of Thoracoscopic Lung Cancer Radical Surgery: A Randomized Controlled Trial.

INTRODUCTION: Ultrasound-guided thoracic paravertebral block (UTPB) is widely used for postoperative analgesia in thoracic surgery. However, it has many disadvantages. Thoracoscopy-guided thoracic paravertebral block (TTPB) is a new technique for thoracic paravertebral block (TPB). In this study, we compared the use of TTPB and UTPB for pain management after thoracoscopic radical surgery for lung cancer. METHODS: In total, 80 patients were randomly divided 1:1 into the UTPB group and the TTPB group. The surgical time of TPB, the success rate of the first puncture, block segment range, visual analog scale (VAS) scores at 2, 6, 12, 24, and 48 h post operation, and the incidence of postoperative adverse reactions were compared between the two groups. RESULTS: The surgical time of TPB was significantly shorter in the TTPB group than in the UTPB group (2.2 ± 0.3 vs. 5.7 ± 1.7 min, t = - 12.411, P < 0.001). The success rate of the first puncture and the sensory block segment were significantly higher in the TTPB group than in the UTPB group (100% vs. 76.9%, χ2 = 8.309, P < 0.001; 6.5 ± 1.2 vs. 5.1 ± 1.3 levels, t = - 5.306, P < 0.001, respectively). The VAS scores were significantly higher during rest and coughing at 48 h post operation than at 2, 6, 12, and 24 h post operation in the TTPB group. The VAS scores were significantly lower during rest and coughing at 12 and 24 h post operation in the TTPB group than in the UTPB group (rest: 2.5 ± 0.4 vs. 3.4 ± 0.6, t = 7.325, P < 0.001; 2.5 ± 0.5 vs. 3.5 ± 0.6, t = 7.885, P < 0.001; coughing: 3.4 ± 0.6 vs. 4.2 ± 0.7, t = 5.057, P < 0.001; 3.4 ± 0.6 vs. 4.2 ± 0.8, t = 4.625, P < 0.001, respectively). No significant difference was observed in terms of postoperative adverse reactions between the two groups. CONCLUSIONS: Compared with UTPB, TTPB shows advantages, such as simpler and more convenient surgery, shorter surgical time, a higher success rate of the first puncture, wider block segments, and superior analgesic effect. TTPB can effectively reduce postoperative pain due to thoracoscopic lung cancer radical surgery. TRIAL REGISTRATION: https://www.chictr.org.cn , identifier ChiCTR2300072005, prospectively registered on 31/05/2023.

A Bibliographic Dataset of Health Artificial Intelligence Research.

Objective: The aim of this study is to construct a curated bibliographic dataset for a landscape analysis on Health Artificial Intelligence (HAI) research. Data Source: We integrated HAI-related bibliographic records, including publications, open research datasets, patents, research grants, and clinical trials from Medline and Dimensions. Methods: Searching: Relevant documents were identified using Medical Subject Headings (MeSH) and Field of Research (FoR) indexed by 2 bibliographic databases, Medline and Dimensions. Extracting: MeSH terms annotated from the aforementioned bibliographic databases served as the primary information for our processing. For document records lacking MeSH terms, we re-extracted them using the Medical Text Indexer (MTI). Mapping: In order to enhance interoperability, HAI multi-documents were organized using a mapping system incorporating MeSH, FoR, The International Classification of Diseases (ICD-10), and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). Integrating: All documents were curated based on a pre-defined ontology of health problems and AI technologies from the MeSH hierarchy. Results: We collected 96,332 HAI documents (publications: 75,820, open research datasets: 638, patents: 11,226, grants: 6,113, and clinical trials: 2,535) during 2009 to 2021. On average, 75.12% of the documents were tagged with at least one label related to either health problems or AI technologies (with 92.9% of publications tagged). Summary: This study presents a comprehensive pipeline for processing and curating HAI bibliographic documents following the FAIR (Findable, Accessible, Interoperable, Reusable) standard, offering a valuable multidimensional collection for the community. This dataset serves as a crucial resource for horizontally scanning the funding, research, clinical assessments, and innovations within the HAI field.

A pragmatic randomized controlled trial to evaluate the efficacy and safety of an oral short-course regimen including bedaquiline for the treatment of patients with multidrug-resistant tuberculosis in China: study protocol for PROSPECT.

INTRODUCTION: The lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China. METHODS: This phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18-65 years) in China. The trial design mainly mirrors that of the "Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB" (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority. DISCUSSION: PROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.

Tyrosine phosphatase SHP2 aggravates tumor progression and glycolysis by dephosphorylating PKM2 in gastric cancer.

Gastric cancer (GC) is among the most lethal human malignancies, yet it remains hampered by challenges in fronter of molecular-guided targeted therapy to direct clinical treatment strategies. The protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) is involved in the malignant progression of GC. However, the detailed mechanisms of the posttranslational modifications of SHP2 remain poorly understood. Herein, we demonstrated that an allosteric SHP2 inhibitor, SHP099, was able to block tumor proliferation and migration of GC by dephosphorylating the pyruvate kinase M2 type (PKM2) protein. Mechanistically, we found that PKM2 is a bona fide target of SHP2. The dephosphorylation and activation of PKM2 by SHP2 are necessary to exacerbate tumor progression and GC glycolysis. Moreover, we demonstrated a strong correlation between the phosphorylation level of PKM2 and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in GC cells. Notably, the low phosphorylation expression of AMPK was negatively correlated with activated SHP2. Besides, we proved that cisplatin could activate SHP2 and SHP099 increased sensitivity to cisplatin in GC. Taken together, our results provide evidence that the SHP2/PKM2/AMPK axis exerts a key role in GC progression and glycolysis and could be a viable therapeutic approach for the therapy of GC.

A computable biomedical knowledge system: Toward rapidly building candidate-directed acyclic graphs.

AIM: It is essential for health researchers to have a systematic understanding of third-party variables that influence both the exposure and outcome under investigation, as shown by a directed acyclic graph (DAG). The traditional construction of DAGs through literature review and expert knowledge often needs to be more systematic and consistent, leading to potential biases. We try to introduce an automatic approach to building network linking variables of interest. METHODS: Large-scale text mining from medical literature was utilized to construct a conceptual network based on the Semantic MEDLINE Database (SemMedDB). SemMedDB is a PubMed-scale repository of the "concept-relation-concept" triple format. Relations between concepts are categorized as Excitatory, Inhibitory, or General. RESULTS: To facilitate the use of large-scale triple sets in SemMedDB, we have developed a computable biomedical knowledge (CBK) system (https://cbk.bjmu.edu.cn/), a website that enables direct retrieval of related publications and their corresponding triples without the necessity of writing SQL statements. Three case studies were elaborated to demonstrate the applications of the CBK system. CONCLUSIONS: The CBK system is openly available and user-friendly for rapidly capturing a set of influencing factors for a phenotype and building candidate DAGs between exposure-outcome variables. It could be a valuable tool to reduce the exploration time in considering relationships between variables, and constructing a DAG. A reliable and standardized DAG could significantly improve the design and interpretation of observational health research.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

A stable Zr(IV)-MOF for efficient removal of trace SO2 from flue gas in dry and humid conditions.

Obtaining suitable adsorbents for selective separation of SO2 from flue gas still remains an important issue. A stable Zr(IV)-MOF (Zr-PTBA) can be conveniently synthesized through the self-assembly of a tetracarboxylic acid ligand (H4L = 4,4',4'',4'''-(1,4-phenylenebis(azanetriyl))tetrabenzoic acid) and ZrCl4 in the presence of trace water. It exhibits a three-dimensional porous structure. The BET surface area is 1112.72 m2/g and the average pore size distribution focus on 5.9, 8.0 and 9.3 Å. Interestingly, Zr-PTBA shows selective adsorption of SO2. The maximum uptake reaches 223.21 cm3/g at ambient condition. While it exhibits lower adsorption uptake of CO2 (30.50 cm3/g) and hardly adsorbs O2 (2.57 cm3/g) and N2 (1.31 cm3/g). Higher IAST selectivities of SO2/CO2 (21.9), SO2/N2 (912.7), SO2/O2 (2269.9) and SO2/CH4 (85.0) have been obtained, which reveal its' excellent gas separation performance. Breakthrough experiment further confirms its application for flue gas deep desulfurization both in dry and humid conditions. Furthermore, the gas adsorption results and mechanisms have also been studied by theoretical calculations.

Stable Anion Exchange Membrane Bearing Quinuclidinium for High-performance Water Electrolysis.

Anion exchange membranes (AEMs) are core components in anion exchange membrane water electrolyzers (AEM-WEs). However, the stability of functional quaternary ammonium cations, especially under high temperatures and harsh alkaline conditions, seriously affects their performance and durability. Herein, we synthesized a 1-methyl-3,3-diphenylquinuclidinium molecular building unit. Density functional theory (DFT) calculations and accelerated aging analysis indicated that the quinine ring structure was exceedingly stable, and the SN2 degradation mechanism dominated. Through acid-catalyzed Friedel-Crafts polymerization, a series of branched poly(aryl-quinuclidinium) (PAQ-x) AEMs with controllable molecular weight and adjustable ion exchange capacity (IEC) were prepared. The stable quinine structure in PAQ-x was verified and retained in the ex situ alkaline stability. Furthermore, the branched polymer structure reduces the swelling rate and water uptake to achieve a tradeoff between dimensional stability and ionic conductivity, significantly improving the membrane's overall performance. Importantly, PAQ-5 was used in non-noble metal-based AEM-WE, achieving a high current density of 8 A cm-2 at 2 V and excellent stability over 2446 h in a gradient constant current test. Based on the excellent alkaline stability of this diaryl-quinuclidinium group, it can be further considered as a multifunctional building unit to create multi-topological polymers for energy conversion devices used in alkaline environments.

Stability of tryptophan-containing LOs in flaxseed oil and their response towards γ-tocopherol.

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.

Synergistic cobalt­copper metal-organic framework anchored amino-functionalized cellulose for antibiotic degradation: Interfacial engineering and mechanism insight.

Improving electron transfer rate of Co species and inhibiting aggregation of metal-organic frameworks (MOFs) particles are essential prerequisites for activating advanced oxidation process in wastewater treatment field. Here, we exploit Cu species with variable valence states to accelerate electron transfer of Co species and then to boost the unsatisfactory degradation efficiency for refractory pharmaceuticals via in-situ growth of copper and cobalt species on l-lysine functionalized carboxylated cellulose nanofibers. Utilizing the synergistic interplay of Co sites and deliberately exposed Cu0/Cu1+ atoms, the subtly designed catalyst exhibited a surprising degradation efficiency (~100 %) toward tetracycline hydrochloride within 10 min (corresponding to a catalytic capacity of 267.71 mg/g) without adjusting temperature and pH. Meanwhile, the catalyst displays good recyclability, well tolerance for coexisting ions and excellent antibacterial performance derived from the intrinsic antibacterial property of Cu-MOF. This research provided a novel strategy to construct MOFs-cellulose materials toward degrading various stubborn antibiotic pollutants.

Biodegradable and multifunctional black mulch film decorated with darkened lignin induced by iron ions for "green" agriculture.

High-value utilization of bleached lignin has been widely used in different fields, whereas the investigation on darkened lignin in composite materials was often ignored. In this work, a sort of eco-friendly and structurally robust sodium carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA)/sodium lignosulfonate (SLS) black composite mulch film was elaborately designed. The chelation and redox reaction effect between Fe ions and SLS lead to the formation of a more quinones structure on lignin, darkening both lignin and the mulch films. The chelation effect between Fe ions and biopolymer formed three-dimensional structures, which can be used as sacrifice bonds to dissipate energy and improve the mechanical properties of the composite films. In particular, the maximum elongation at break and toughness increased from 48.4 % and 1141 kJ/m3 for the CMC/PVA film to 210.9 % and 1426 kJ/m3 for the optimized CMC/PVA/SLS/Fe black mulch film, respectively. In addition, the optimized black mulch film also possesses good soil water retention, thermal preservation effect, controlled urea release, and well biodegradability. This work offered a novel strategy for designing eco-friendly black mulch with reinforced mechanical strength, slow-release urea, soil moisture retention, and heat preservation performances.

[Research progress of relationship in long-novel coronavirus syndrome and sarcopenia].

At present, the major public health challenges caused by novel coronavirus infection have gradually subside. However, a large number of people are still suffering from long-novel coronavirus syndrome or post-novel coronavirus syndrome. The clinical manifestations of long coronavirus syndrome are related to multiple systems, such as respiratory, circulatory, nervous, digestive and musculoskeletal systems, with various long-term persistent symptoms after novel coronavirus infection. At the same time, the infection of the novel coronavirus is an important cause of frailty and sarcopenia in the elderly population. However, at present, the scholars have not paid enough attention to the skeletal muscle weakness caused by the novel coronavirus. Therefore, this paper focuses on the long-novel coronavirus syndrome and sarcopenia to explore the pathological mechanism of skeletal muscle attenuation caused by the SARS-CoV-2 mediated "cytokine storm", mitochondrial damage, hypoxia state and other links,so as to raise the attention of clinical and academic researchers and improve the clinical strategy of frailty and sarcopenia after novel coronavirus infection.

Toward tuberculosis elimination by understanding epidemiologic characteristics and risk factors in Hainan Province, China.

BACKGROUND: The disease burden of tuberculosis (TB) was heavy in Hainan Province, China, and the information on transmission patterns was limited with few studies. This atudy aims to further explore the epidemiological characteristics and influencing factors of TB in Hainan Province, and thereby contribute valuable scientific evidences for TB elimination in Hainan Province. METHODS: The TB notification data in Hainan Province from 2013 to 2022 were collected from the Chinese National Disease Control Information System Tuberculosis Surveillance System, along with socio-economic data. The spatial-temporal and population distributions were analyzed, and spatial autocorrelation analysis was conducted to explore TB notification rate clustering. In addition, the epidemiological characteristics of the cases among in-country migrants were described, and the delay pattern in seeking medical care was investigated. Finally, a geographically and temporally weighted regression (GTWR) model was adopted to analyze the relationship between TB notification rate and socio-economic indicators. The tailored control suggestions in different regions for TB elimination was provided by understanding epidemiological characteristics and risk factors obtained by GTWR. RESULTS: From 2013 to 2022, 64,042 cases of TB were notified in Hainan Province. The estimated annual percentage change of TB notification rate in Hainan Province from 2013 to 2020 was - 6.88% [95% confidence interval (CI): - 5.30%, - 3.69%], with higher rates in central and southern regions. The majority of patients were males (76.33%) and farmers (67.80%). Cases among in-country migrants primarily originated from Sichuan (369 cases), Heilongjiang (267 cases), Hunan (236 cases), Guangdong (174 cases), and Guangxi (139 cases), accounting for 53%. The majority (98.83%) of TB cases were notified through passive case finding approaches, with delay in seeking care. The GTWR analysis showed that gross domestic product per capita, the number of medical institutions and health personnel per 10,000 people were main factors affecting the high TB notification rates in some regions in Hainan Province. Different regional tailored measures such as more TB specialized hospitals were proposed based on the characteristics of each region. CONCLUSIONS: The notification rate of TB in Hainan Province has been declining overall but still remained high in central and southern regions. Particular attention should be paid to the prevalence of TB among males, farmers, and out-of-province migrant populations. The notification rate was also influenced by economic development and medical conditions, indicating the need of more TB specialized hospitals, active surveillance and other tailored prevention and control measures to promote the progress of TB elimination in Hainan Province.

RIRS with FV-UAS vs. MPCNL for 2-3-cm upper urinary tract stones: a prospective study.

To observe the efficacy and safety of retrograde intrarenal surgery (RIRS) combined with flexible vacuum-assisted ureteral access sheath (FV-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 2-3 cm upper urinary tract stones. A total of 160 patients with 2-3 cm upper urinary tract stones were prospectively randomized into 2 groups-80 in the FV-UAS group and 80 cases as control in the MPCNL group. The stone-free rates (SFRs) at different times (postoperative 1st day and 4th week) were considered as the primary outcome of the study. The secondary end points were operative time, hemoglobin decrease, postoperative hospital stay, and operation-related complications. There was no obvious difference between the two groups in patient's demographics and preoperative clinical characteristics (all P > 0.05). Postoperative data showed that mean decrease in hemoglobin level was less in FV-UAS group than that in MPCNL group (5.3 vs. 10.8 g/L, P < 0.001). Postoperative hospital stay in FV-UAS group was more shorten than that in MPCNL group (2.7 vs. 4.9 days, P < 0.001). There was no statistical significance between the two groups in SFRs during postoperative 1st day and 4th week (both P > 0.05). However, in terms of the rates of bleeding and pain, MPCNL group were both significantly higher than FV-UAS group (6.2 vs. 0.0%, P = 0.023; 16.2 vs. 2.5%, P = 0.003; respectively). Our study showed that RIRS with FV-UAS, a new partnership to treat 2-3 cm upper urinary tract stones, was satisfying as it achieved a high SFR rate and a low rate of complications. This method was safe and reproducible in clinical practice.

Design of Optical System for Ultra-Large Range Line-Sweep Spectral Confocal Displacement Sensor.

The spectrum confocal displacement sensor is an innovative type of photoelectric sensor. The non-contact advantages of this method include the capacity to obtain highly accurate measurements without inflicting any harm as well as the ability to determine the object's surface contour recovery by reconstructing the measurement data. Consequently, it has been widely used in the field of three-dimensional topographic measuring. The spectral confocal displacement sensor consists of a light source, a dispersive objective, and an imaging spectrometer. The scanning mode can be categorized into point scanning and line scanning. Point scanning is inherently present when the scanning efficiency is low, resulting in a slower measurement speed. Further improvements are necessary in the research on the line-scanning type. It is crucial to expand the measurement range of existing studies to overcome the limitations encountered during the detection process. The objective of this study is to overcome the constraints of the existing line-swept spectral confocal displacement sensor's limited measuring range and lack of theoretical foundation for the entire system. This is accomplished by suggesting an appropriate approach for creating the optical design of the dispersive objective lens in the line-swept spectral confocal displacement sensor. Additionally, prism-grating beam splitting is employed to simulate and analyze the imaging spectrometer's back end. The combination of a prism and a grating eliminates the spectral line bending that occurs in the imaging spectrometer. The results indicate that a complete optical pathway for the line-scanning spectral confocal displacement sensor has been built, achieving an axial resolution of 0.8 µm, a scanning line length of 24 mm, and a dispersion range of 3.9 mm. This sensor significantly expands the range of measurements and fills a previously unaddressed gap in the field of analyzing the current stage of line-scanning spectral confocal displacement sensors. This is a groundbreaking achievement for both the sensor itself and the field it operates in. The line-scanning spectral confocal displacement sensor's design addresses a previously unmet need in systematic analysis by successfully obtaining a wide measuring range. This provides systematic theoretical backing for the advancement of the sensor, which has potential applications in the industrial detection of various ranges and complicated objects.

Protective effect against toxoplasmosis in BALB/C mice vaccinated with recombinant Toxoplasma gondii CDPK3, GRA35, and ROP46 protein cocktail vaccine.

Toxoplasma gondii (T. gondii) is one of the most common pathogenic protozoa in the world, and causes toxoplasmosis, which in varying degrees causes significant economic losses and poses a serious public health challenge globally. To date, the development of an effective vaccine for human toxoplasmosis remains a challenge. Given that T.gondii calcium-dependent protein kinase 3 (CDPK3), dense granule protein 35 (GRA35) and rhoptry organelle protein 46 (ROP46) play key roles during Toxoplasma gondii invasion of host cells, we developed a protein vaccine cocktail including these proteins and validated its protective efficacy. The specific protective effects of vaccine on mice were analyzed by measuring serum antibodies, cytokines, splenocyte proliferation, the percentage of CD4+ and CD8+ T-lymphocytes, survival rate, and parasite cyst burden. The results showed that mice vaccinated with a three-protein cocktail produced the highest levels of immune protein antibodies to IgG, and high levels of IFN-γ, IL-2, IL-4, and IL-10 compared to other mice vaccinated with two proteins. In addition, CD4+ and CD8+ T cell percentages were significantly elevated. Compared to the control groups, mice vaccinated with the three-protein cocktail survived significantly longer after acute infection with T. gondii and had significantly fewer cysts after chronic infection. These results demonstrated that a cocktail vaccine of TgCDPK3, TgGRA35, and TgROP46 can effectively induce cellular and humoral immune responses with good protective effects in mice, indicating its potential as vaccine candidates for toxoplasmosis.

Constructing high-density crack-microstructures within MXene interlayers for ultrasensitive and superhydrophobic cellulosic fibers-based sensors.

Incorporating biopolymers into two-dimensional transition metal carbides and/or nitrides (2D MXene) has been demonstrated as an effective strategy to improve the mechanical behaviors of MXene-based composites. However, the insulate nature of biopolymers inevitably deteriorated the electrical conductivity and the sensitivity of assembled sensors. Herein, a novel cellulose nanofiber (CNF)/MXene/carbon black (CB) composite was demonstrated as the conductive layer in eco-friendly cellulose paper-based sensors by intercalating the CB into the MXene/CNF interlayer, followed by coating hydrophobic SiO2 for encapsulation. Befitting from the high-density crack-microstructures between CB and MXene, the fabricated superhydrophobic paper CB/CNF/MXene/SiO2 sensor delivered ultrahigh sensitivity of 729.52 kPa-1, low detect limit of 0.29 Pa, rapid response time of 80 ms and excellent stability over 10,000 cycles. Moreover, the fabricated sensor was capable of detecting the physiological parameter of human (e.g. huge/subtle movements) and spatial pressure distribution. Furthermore, the presence of SiO2 layer endowed the sensor with superhydrophobic performance (water contact angle ∼158.2 o) and stable electrical signals under high moisture conditions or even under water. Our work proposed a novel strategy to boost the sensitivity of MXene-based conductive layer in flexible electronic devices.

Protozoan-Derived Cytokine-Transgenic Macrophages Reverse Hepatic Fibrosis.

Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage-based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor-transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN-γ-treated macrophages, making macrophage-based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF-κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.

Bioconversion of spray corn husks into L-lactic acid with liquid hot water pretreatment.

Agricultural by-products like rice husk, bran, and spray corn husks, often utilized as feed, are considered less desirable. This study aims to enhance the utilization rate of these materials by subjecting then to liquid hot water (LHW) pretreatment, followed by enzymatic hydrolysis to produce fermentable sugars. We investigated the production of L-lactic acid using two methods: simultaneous saccharification fermentation (SSF) and separate hydrolysis fermentation (SHF), following varying intensities of LHW pretreatment. The results showed that the optimal enzymatic hydrolysis efficiency was achieved from spray corn husks under the pretreatment conditions of 155 °C and 15 min. SHF was generally more effective than SSF. The glucose L-lactic acid conversion rate in SHF using spray corn husks can reach more than 90 %. Overall, this work proposed a novel, environmental-friendly strategy for efficient and for L- lactic acid production from spray corn husks.

Bright, photostable and long-circulating NIR-II nanoparticles for whole-process monitoring and evaluation of renal transplantation.

Kidney transplantation is the gold standard for the treatment of end-stage renal diseases (ESRDs). However, the scarcity of donor kidneys has caused more and more ESRD patients to be stuck on the waiting list for transplant surgery. Improving the survival rate for renal grafts is an alternative solution to the shortage of donor kidneys. Therefore, real-time monitoring of the surgical process is crucial to the success of kidney transplantation, but efficient methods and techniques are lacking. Herein, a fluorescence technology based on bright, photostable and long-circulating aggregation-induced emission (AIE) active NIR-II nano-contrast agent DIPT-ICF nanoparticles for the whole-process monitoring and evaluation of renal transplantation has been reported. In the aggregated state, DIPT-ICF exhibits superior photophysical properties compared with the commercial dyes IR-26 and IR-1061. Besides, the long-circulating characteristic of the AIE nano-contrast agent helps to achieve renal angiography in kidney retrieval surgery, donor kidney quality evaluation, diagnosing vascular and ureteral complications, and assessment of renal graft reperfusion beyond renovascular reconstruction, which considerably outperforms the clinically approved indocyanine green (ICG).