Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors.

The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs in this domain. Their investigation reveals the pronounced augmentation of anti-tumor activity in CAR T cells through the introduction of a T cell neoplasm fusion gene, CARD11-PIK3R3. The incorporation of this gene into engineered T cell therapy holds promise as a formidable tool in the arsenal of cancer immunotherapy. The innovative strategy outlined not only mitigates the requirement for high doses of CAR T cells but also enhances tumor control while exhibiting encouraging safety profiles. The exploration of the CARD11-PIK3R3 fusion gene represents an advancement in our approach to bolstering the anti-tumor efficacy of immunotherapeutic interventions. Nonetheless, the imperative for further inquiry to ascertain its transfection efficiency and long-term safety cannot be overstated. Nevertheless, this seminal investigation offers a beacon of hope in surmounting the formidable treatment impediments posed by solid tumors, paving the way for a transformative era in cancer therapeutics.

Effects of the three amendments on NH3 volatilization, N2O emissions, and nitrification at four salinity levels: An indoor experiment.

The marked salinity and alkaline pH of coastal saline soil profoundly impact the nitrogen conversion process, leading to a significantly reduced nitrogen utilization efficiency and substantial gaseous nitrogen loss. The application of soil amendments (e.g. biochar, manure, and gypsum) was proved to be effective for the remediation of saline soils. However, the effects of the three amendments on soil nitrogen transformation in soils with various salinity levels, especially on NH3 volatilization and N2O emission, remain elusive. Here, we reported the effects of biochar, manure, and gypsum on NH3 volatilization and N2O emission under four natural salinity gradients in the Yellow River Delta. Also, high-throughput sequencing and qPCR analysis were performed to characterize the response of nitrification (amoA) and denitrification (nirS, nirK, and nosZ) functional genes to the three amendments. The results showed that the three amendments had little effect on NH3 volatilization in low- and moderate-salinity soils, while biochar stimulated NH3 volatilization in high-salinity soils and reduced NH3 volatilization in severe-salinity soils. Spearman correlation analysis demonstrated that AOA was significantly and positively correlated with the NO3--N content (r = 0.137, P < 0.05) and N2O emissions (r = 0.174, P < 0.01), which indicated that AOA dominated N2O emissions from nitrification in saline soils. Structural equation modeling indicated that biochar, manure, and gypsum affected N2O emission by influencing soil pH, conductivity, mineral nitrogen content, and functional genes (AOA-amoA and nosZ). Two-way ANOVA further showed that salinity and amendments (biochar, manure, and gypsum) had significant effects on N2O emissions. In summary, this study provides valuable insights to better understand the effects of gaseous N changes in saline soils, thereby improving the accuracy and validity of future GHG emission predictions and modeling.

Association between organophosphate esters exposure and all-cause and cause-specific mortality: a national population-based cohort study.

Exposure to organophosphate esters (OPEs) is associated with several chronic diseases, but the relationship with mortality risk is unclear. Therefore, we used the National Health and Nutrition Examination Survey 2011-2018 data to evaluate these relationships. 6,869 participants aged 18 years or older were included. Survival status information was obtained through the National Death Index through 31 December 2019. Multivariable COX regression model was adopted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships of urinary OPEs metabolites with mortality risk. During an average of 5.0 years of follow-up, 406 deaths were documented. After adjusting for confounders, bis(2-chloroethyl) phosphate was associated with an increased risk of all-cause mortality [HR (95%CI) = 1.12(1.05-1.20)] and cardiovascular mortality [HR (95%CI) = 1.15(1.04-1.26)]. Our study found that exposure to OPEs was significantly associated with increased risks of all-cause and cardiovascular mortality. Consequently, controlling OPEs exposure is needed to alleviate the health-related burden.

The role of transforming growth factor beta-1 protein in Escherichia coli secondary infection induced by H9N2 avian influenza virus in chickens.

The H9N2 subtype of avian influenza virus (AIV) is common in poultry production. It causes mild clinical signs but rarely leads to poultry mortalities. However, higher mortality can occur in chickens with co-infections, especially avian pathogenic Escherichia coli (APEC), which results in huge economic losses for the poultry industry. Unfortunately, the mechanism of co-infection remains unknown. Our previous studies screened several proteins associated with bacterial adhesion, including transforming growth factor beta-1 (TGF-ß1), integrins, cortactin, E-cadherin, vinculin, and fibromodulin. Herein, we investigated the contribution of TGF-ß1 to APEC adhesion after H9N2 infection. We first infected H9N2 and APEC in chicken, chicken embryo and DF-1 cells, and demonstrated that H9N2 infection promotes APEC adhesion to hosts in vitro and in vivo by plate count method. Through real-time fluorescence quantification and enzyme-linked immunosorbent assay, it was demonstrated that H9N2 infection not only increases TGF-ß1 expression but also its activity in a time-dependent manner. Then, through exogenous addition of TGF-ß1 and overexpression, we further demonstrated that TGF-ß1 can increase the adhesion of endothelial cells to DF-1 cells. Furthermore, the capacity of APEC adhesion to DF-1 cells was significantly decreased either by adding a TGF-ß1 receptor inhibitor or using small interfering RNAs to interfere with the expression of TGF-ß1. To sum up, H9N2 infection can promote the upregulation of TGF-ß1 and then increase the adhesion ability of APEC. Targeting TGF-ß1 and its associated pathway will provide valuable insights into the clinical treatment of E. coli secondary infection induced by H9N2 infection.

Effect of duck interferon-α and an anti-cap protein polyclonal antibody against duck circovirus.

Duck circovirus (DuCV) is one of the most prevalent viruses in the duck breeding industry, and causes persistent infection and severe immunosuppression. Currently, there is a serious lack of prevention and control measures and no commercial vaccine against DuCV. Therefore, effective antiviral drugs are important for treating DuCV infection. Interferon (IFN) is an important component of antiviral innate immunity, but it remains unclear whether duck IFN-α has a clinical effect against DuCV. Antibody therapy is an important way to treat viral infections. The DuCV structural protein (cap) is immunogenic, and it remains to be determined whether an anti-cap protein antibody can effectively block DuCV infection. In this study, the duck IFN-α gene and the DuCV structural protein cap gene were cloned, expressed and purified in Escherichia coli to prepare duck recombinant IFN-α and the cap protein. Then, rabbits were immunized with the recombinant cap protein to prepare a rabbit polyclonal antibody. This study investigated the antiviral effect of duck recombinant IFN-α and the anti-cap protein antibody and their combined effect on Cherry Valley ducks infected with DuCV. The results showed that the treatment significantly alleviated the clinical symptoms of immune organ atrophy and immunosuppression compared with the control. The histopathological damage of the target organs was alleviated, and replication of DuCV in the immune organs was significantly inhibited. The treatment also reduced the damage caused by DuCV to the liver and immune function, and increased the level of the DuCV antibody in the blood, thereby improving antiviral activity. Notably, the combination of duck IFN-α and the polyclonal antibody completely blocked DuCV infection after 13 days under the experimental conditions, showing a better inhibitory effect on DuCV infection than single treatments. These results showed that duck recombinant IFN-α and the anti-cap protein antibody can be used as antiviral drugs to clinically treat and control DuCV infection, particularly the vertical transmission of the virus in breeding ducks.

L-Cysteine-Modified Transfersomes for Enhanced Epidermal Delivery of Podophyllotoxin.

The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention (p < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.

Alkene Synthesis by Photo-Wolff-Kischner Reaction of Sulfur Ylides and N-Tosylhydrazones.

A visible-light-driven and room temperature photo-Wolff-Kischner reaction of sulfur ylides and N-tosylhydrazones has been developed for the first time to provide modular access to alkene synthesis. The high functional group tolerance and broad substrate scope were demonstrated by more than 60 examples. Both E- and Z-olefinic stereochemistry in the products could be controlled with excellent stereoselectivity. A series of mechanistic studies support that the reaction should proceed through a radical-carbanion crossover pathway, specifically involving addition of photo-generated sulfur ylide radical cations to N-tosylhydrazones to form carbanions and subsequent Wolff-Kischner process.

Elevated mature monocytes in bone marrow accompanied with a higher IPSS-R score predicts a poor prognosis in myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. Clinically, elevated mature monocyte in bone marrow is often observed, but its clinical value still remains unclear. METHODS: We retrospectively analyzed a cohort of 216 MDS patients to explore the prognostic value of the percentage of mature monocyte in bone marrow (PMMBM). All patients were divided into elevated PMMBM group and the normal group by 6% PMMBM as the cut-off value. RESULTS: Our results showed that PMMBM> 6% was associated with inferior overall survival (OS) (P = 0.026) along with higher-risk IPSS-R (P = 0.025) and higher frequency of IDH2 mutation (P = 0.007). Multivariate analyses showed that besides older age (> 60 years) for OS, gender (male) for OS, lower neutrophil count (< 0.8 ×  109/L) for OS, higher bone marrow blast percentage (> 5%) for OS and LFS, poorer karyotype for OS, elevated PMMBM was also an independent adverse prognostic factor for OS in MDS (P < 0.0001) but not for LFS (P = 0.736). CONCLUSIONS: These findings indicate that increased PMMBM may assists Revised International Prognostic Scoring System (IPSS-R) to predict a poor outcome and provide a novel evaluation factor for MDS patients especially when their karyotype analyses fail.

A needle-type micro-sampling device for collecting nanoliter sap sample from plants.

In plant research, measuring the physiological parameters of plants is vital for understanding the behavior and response of plants to changes in the external environment. Plant sap analysis provides an approach for elucidating the physiological condition of plants. However, to facilitate accurate sap analysis, a sampling device capable of collecting sap samples from plants is required. In this paper, a minimally invasive, needle-type micro-sampling device capable of collecting nanoliter (~ 91 nL) quantities of sap from plants is described. The developed micro-sampling system showed great reproducibility (3%) in experiments designed to assess sampling performance. As a proof of concept, sap samples were collected continuously from target plants with the micro-sampling system, and the dynamic changes in potassium ions, plant hormones and sugar levels inside plants were analyzed. The results demonstrated the feasibility of the micro-sampling device and its potential for developing a measurement system for plant research in the future.

Bioactive monoterpene phenol dimers from the fruits of Psoralea corylifolia L.

Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1-9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1-9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1-4) were composed of two bakuchiols, one of which was cyclized via a C-7'/ C-12' single bond to form a six-member ring, and connect to each other by C-4-O-C-13' bonds. Bisbakuchiols (7-9) had a pyran ring by linkage of C-8-O-C-12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC50 values of 0.69 and 0.73 µM, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from -6.9 to -7.1 kcal/mol.

Destruction of Per- and Polyfluoroalkyl Substances (PFAS) with Advanced Reduction Processes (ARPs): A Critical Review.

Advanced reduction processes (ARPs) have emerged as a promising method for destruction of persistent per- and polyfluoroalkyl substances (PFAS) in water due to the generation of short-lived and highly reductive hydrated electrons (eaq-). This study provides a critical review on the mechanisms and performance of reductive destruction of PFAS with eaq-. Unique properties of eaq- and its generation in different ARP systems, particularly UV/sulfite and UV/iodide, are overviewed. Different degradation mechanisms of PFAS chemicals, such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), and others (e.g., short chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs), per- and polyfluoro dicarboxylic acids, and fluorotelomer carboxylic acids), are reviewed, discussed, and compared. The degradation pathways of these PFAS chemicals rely heavily upon their head groups. For specific PFAS types, fluoroalkyl chain lengths may also affect their reductive degradation patterns. Degradation and defluorination efficiencies of PFAS are considerably influenced by solution chemistry parameters and operating factors, such as pH, dose of chemical solute (i.e., sulfite or iodide) for eaq- photoproduction, dissolved oxygen, humic acid, nitrate, and temperature. Furthermore, implications of the state-of-the-art knowledge on practical PFAS control actions in water industries are discussed and the priority research needs are identified.

Study of oxygen evolution reaction on amorphous Au13@Ni120P50 nanocluster.

The pursuit of catalysts to promote effective water oxidization to produce oxygen has become a research subject of high priority for water splitting. Here, first-principles calculations are employed to study the water-splitting oxygen evolution reaction (OER) on ∼1.5 nm diameter Au13@Ni120P50 core-shell nanoclusters. Water splitting to produce oxygen proceeds in four intermediate reaction steps (OH*, O*, OOH* and O2). Adsorption configurations and adsorption energies for the species involved in OER on both Au13@Ni120P50 cluster and Ni12P5(001) supported by Au are presented. In addition, thermodynamic free energy diagrams and kinetic potential energy changes are systematically discussed. We show that the third intermediate reaction (O* reacting with H2O to produce OOH*) of the four elementary steps is the reaction-determining step, which accords with previous results. Also, the catalytic performance of OER for Au13@Ni120P50 is better than that for Ni12P5(001) supported by Au in terms of reactive overpotential (0.74 vs. 1.58 V) and kinetic energy barrier (2.18 vs. 3.17 eV). The optimal kinetic pathway for OER is further explored carefully for the Au13@Ni120P50 cluster. The low thermodynamic overpotential and kinetic energy barrier make Au13@Ni120P50 promising for industrial applications as a good OER electrocatalyst candidate.

Gold Nanoprobe-Enabled Three-Dimensional Ozone Imaging by Optical Coherence Tomography.

Ozone (O3) would be harmful to human skin for its strong oxidizing property, especially when stratum corneum or corneal epithelium is wounded. Imaging the penetration and distribution of ozone at depth is beneficial for studying the influence of ozone on skin or eyes. Here, we introduced a facile method for three-dimensional (3D) imaging of the penetration of O3 into the anterior chamber of an isolated crucian carp eye by using optical coherence tomography (OCT) combined with gold triangular nanoprisms (GTNPs) as the contrast agent and molecular probe. We illustrated the specific response of GTNPs to ozone and demonstrated that GTNPs can function as an efficient nanoprobe for sensing O3. The stabilities of GTNPs in different biologic solutions, as well as the signal intensity of GTNPs on an OCT imaging system, were investigated. Visualization of 3D penetration and distribution of O3 in the biologic tissue was proved for the first time. The quantitative analysis of O3 diffusion in the anterior chamber of the fish eye revealed a penetration depth of 311 µm within 172 min. Due to the strong scattering, near-infrared extinction band, and easy functionalization of GTNPs, they could further serve as nanoprobes for 3D OCT or multimodal imaging of other molecules or ions in the future.

Plasmonic Nanoprobe of (Gold Triangular Nanoprism Core)/(Polyaniline Shell) for Real-Time Three-Dimensional pH Imaging of Anterior Chamber.

Three-dimensional (3D) molecular imaging enables the study of biological processes in both living and nonviable systems at the molecular level and has a high potential on early diagnosis. In conjunction with specific molecular probes, optical coherent tomography (OCT) is a promising imaging modality to provide 3D molecular features at the tissue level. In this study, we introduced (gold triangular nanoprism core)/(polyaniline shell) nanoparticles (GTNPs@PANI) as an OCT contrast agent and pH-responsive nanoprobe for 3D imaging of pH distribution. These core/shell nanoparticles possessed significantly different extinction and scattering properties in acidic and basic microenvironments. The switch of the optical features of the nanoparticles upon pH change was reversible, and the response time was less than 1.0 s. The nanoprobe successfully indicated the acid regions of a mimic tumor from the basic region in a gelatin-based phantom under OCT imaging. As a demonstration of practical applications, real-time 3D OCT imaging of pH and lactic acid in the anterior chamber of a fish eye was realized by GTNPs@PANI nanoparticles. Using GTNPs@PANI nanoparticles as the contrast probes for OCT imaging, noninvasive and real-time molecular imaging in both living and nonviable systems at the microscale can be achieved.

Size-dependent concentrations of thermal vacancies in solid films.

Solid films are considered as typical model systems to study size effects on thermal vacancy concentration in nanomaterials. By combining the generalized Young-Laplace equation with the chemical potential of vacancies, a strict size-dependent thermodynamic model of vacancies, which includes the surface intrinsic elastic parameters of the eigenstress, Young's modulus and the geometric size of the solid films, was established. The vacancy concentration changes in the film with respect to the bulk value, depending on the geometric size and surface stress sign of the solid films. Atomistic simulations of Au and Pt films verified the developed thermodynamic model. These results provide physical insights into the size-dependent thermal vacancy concentration in nanomaterials.

Risk assessment of toxic metals in street dust from a medium-sized industrial city of China.

The concentrations of toxic metals As, Co, Cr, Cu, Mn, Ni, Pb, V and Zn in street dust of Tongchuan, China were determined by wavelength dispersive X-ray fluorescence spectrometry. The risk of the analyzed metals to urban ecosystem and human health were evaluated by potential ecological risk index and human exposure model, respectively. The results show that, in comparison with Shaanxi soil, dust samples have elevated metal concentration as a whole expect for As, Mn, V and Ni. The assessment results of ecological risk indicate that the ecological risks of As, Cr, Mn, Ni, Cu, V and Zn in the dust were in the low level, while Pb and Co presented low to moderate level. Health risk assessment shows that ingestion was the main exposure route of all analyzed toxic metals in street dust to children and adults. The non-cancer risks of the studied metals to children and adults were within the safe range, and the cancer risks of As, Co, Cr and Ni were also within the currently acceptable range.

Microplastics release from face masks: Characteristics, influential factors, and potential risks.

Since the COVID-19 pandemic, face masks have been used popularly and disposed of improperly, leading to the generation of a large amount of microplastics. The objective of this review is to provide a comprehensive insight into the characteristics of mask-derived microplastics, the influential factors of microplastics release, and the potential risks of these microplastics to the environment and organisms. Mask-derived microplastics were predominantly transparent fibers, with a length of <1 mm. The release of microplastics from masks is mainly influenced by mask types, use habits, and weathering conditions. Under the same conditions, surgical masks release more microplastics than other types of masks. Long-term wearing of masks and the disinfection for reuse can promote the release of microplastics. Environmental media, UV irradiation, temperature, pH value, and mechanical shear can also influence the microplastics release. The risks of mask-derived microplastics to human health via inhalation cannot be neglected. Future studies should pay more attention to the release of microplastics from the masks with alternative materials and under more weathering conditions.

Semaphorin 3 a restores the ability of type 1 regulatory T cells to suppress food allergy.

Food allergy (FA) is a common immune disorder that involves dysfunctional immune regulation. More remedies for restoring immune regulation are necessary. Semaphorin 3 A (Sema3a) is a secreted protein of the semaphorin family, which plays a role in immune responses at all stages. The objective of this study is to gain an understanding of how Sema3a can restore the immune regulatory abilities of type 1 regulatory T cells (Tr1 cells). In this study, blood samples were taken from patients with FA. Tr1 cells were purified from blood samples using flow cytometry cell sorting, using LAG3 and CD49b as surface markers. RNA sequencing was employed to examine the characteristics of Tr1 cells. We observed an exaggerated increase in ER stress in peripheral Tr1 cells of FA patients. Enforced expression of spliced X-box protein-1 (XBP1s, one of the key molecules in ER stress) resulted in suppression of interleukin (IL)-10 expression in CD4+ T cells. Eukaryotic initiation factor 2a (eIF2a) mediated the effects of XBP1 on suppressing IL-10 expression in Tr1 cells. The use of Sema3a resulted in a decrease in ER stress, and an increase in IL-10 expression in Tr1 cells of FA patients. Sema3a administration reduced experimental FA by increasing the number of Tr1 cells. In conclusion, IL-10 expression in Tr1 cells is disturbed by ER stress. Sema3a treatment restores the expression of IL-10 and the immunosuppressive capability of Tr1 cells.

Single-atom Mn-embedded carbon nitride as highly efficient peroxymonosulfate catalyst for the harmful algal blooms control.

In recent years, water quality deterioration caused by harmful algal blooms (HABs) has become one of the global drinking water safety issues, and sulfate radical driven heterogeneous advanced oxidation technology has been widely used for algae removal. However, the shortages of low active site exposure, metal leaching, and secondary contamination limit its further application. Therefore, the single-atom Mn anchored on inorganic carbon nitride was constructed to enhance the oxidation and coagulation of algal cells while maintaining cell integrity in this study. The removal efficiency of Microcystis aeruginosa was as high as 100 % within 30 min under the optimal conditions of 400 mg/L single-atom Mn-embedded g-C3N4 (SA-MCN) and 0.32 mM peroxymonosulfate (PMS). Importantly, the K+ release, malondialdehyde concentration, floccules morphology and variation of algal organic matters further showed that the algal cells still maintained high integrity without severe rupture during the catalytic reaction. Furthermore, the catalytic mechanisms of algae removal by moderate oxidation and simultaneous coagulation in this system were explored by quenching experiments, EPR analysis, theoretical calculation, and Zeta potential. In brief, this study highlighted the single-atom heterogeneous catalyst with high-efficiency and environmental-friendliness in harmful algal blooms control.

Zirconium ion mediated collagen nanofibrous hydrogels with high mechanical strength.

Low mechanical strength is still the key question for collagen hydrogel consisting of nanofibrils as hard tissue repair scaffolds with no loss of biological function. In this work, novel collagen nanofibrous hydrogels with high mechanical strength were fabricated based on the pre-protection of trisodium citrate masked Zr(SO4)2 solution for collagen self-assembling nanofibrils and then further coordination with Zr(SO4)2 solution. The mature collagen nanofibrils with d-period were observed in Zr(IV) mediated collagen hydrogels by AFM when the Zr(IV) concentration was ≥ 10 mmol/L, and the distribution of zirconium element was uniform. Due to the coordination of Zr(IV) with ─COOH, ─NH2 and ─OH within collagen and the tighter entanglement of collagen nanofibrils, the elastic modulus and compressive strength of Zr(IV) mediated collagen nanofibrous hydrogel were 208.3 and 1103.0 kPa, which were approximate 77 and 12 times larger than those of pure collagen hydrogel, respectively. Moreover, the environmental stability such as thermostability, swelling ability and biodegradability got outstanding improvements and could be regulated by Zr(IV) concentration. Most importantly, the resultant hydrogel showed excellent biocompatibility and even accelerated cell proliferation.