The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.

Non-epitaxial single-crystal 2D material growth by geometric confinement.

Two-dimensional (2D) materials and their heterostructures show a promising path for next-generation electronics1-3. Nevertheless, 2D-based electronics have not been commercialized, owing mainly to three critical challenges: i) precise kinetic control of layer-by-layer 2D material growth, ii) maintaining a single domain during the growth, and iii) wafer-scale controllability of layer numbers and crystallinity. Here we introduce a deterministic, confined-growth technique that can tackle these three issues simultaneously, thus obtaining wafer-scale single-domain 2D monolayer arrays and their heterostructures on arbitrary substrates. We geometrically confine the growth of the first set of nuclei by defining a selective growth area via patterning SiO2 masks on two-inch substrates. Owing to substantial reduction of the growth duration at the micrometre-scale SiO2 trenches, we obtain wafer-scale single-domain monolayer WSe2 arrays on the arbitrary substrates by filling the trenches via short growth of the first set of nuclei, before the second set of nuclei is introduced, thus without requiring epitaxial seeding. Further growth of transition metal dichalcogenides with the same principle yields the formation of single-domain MoS2/WSe2 heterostructures. Our achievement will lay a strong foundation for 2D materials to fit into industrial settings.

The potential utility of dendritic fibrous nanosilica as an adsorbent and a catalyst in carbon capture, utilization, and storage.

Anthropogenic emissions of greenhouse gases (GHG; e.g., CO2) are regarded as the most critical cause of the current global climate crisis. To combat this issue, a plethora of CO2 capture, utilization, and storage (CCUS) technologies have been proposed and developed based on a number of technical principles (e.g., post-combustion capture, chemical looping, and catalytic conversion). In this light, the potential utility of dendritic fibrous nanosilica (DFNS) materials is recognized for specific CCUS applications (such as adsorptive capture of CO2 and its catalytic conversion into a list of value-added products (e.g., methane, carbon monoxide, and cyclic carbonates)) with the highly tunable properties (e.g., high surface area, pore volume, multifunctional surface, and open pore structure). This review has been organized to offer a comprehensive evaluation of the approaches required for tuning the textural/morphological/surface properties of DFNS (based on multiple synthesis and modification scenarios) toward CCUS applications. It further discusses the effects of such approaches on the properties of DFNS materials in relation to their CCUS performance. This review is thus expected to help develop and implement advanced strategies for DFNS-based CCUS technologies.

Tumor immunogenicity regulates host immune responses, and conventional dendritic cell type 2 uptakes the majority of tumor antigens in an orthotopic lung cancer model.

Human lung cancer carries high genetic alterations, expressing high tumor-specific neoantigens. Although orthotopic murine lung cancer models recapitulate many characteristics of human lung cancers, genetically engineered mouse models have fewer somatic mutations than human lung cancer, resulting in scarce immune cell infiltration and deficient immune responses. The endogenous mouse lung cancer model driven by Kras mutation and Trp53 deletion (KP model) has minimal immune infiltration because of a scarcity of neoantigens. Fine-tuning tumor antigenicity to trigger the appropriate level of antitumor immunity would be key to investigating immune responses against human lung cancer. We engineered the KP model to express antigens of OVA peptides (minOVA) as neoantigens along with ZsGreen, a traceable fluorescent conjugate. The KP model expressing minOVA exhibited stronger immunogenicity with higher immune cell infiltration comprised of CD8+ T cells and CD11c+ dendritic cells (DCs). Consequently, the KP model expressing minOVA exhibits suppressed tumor growth compared to its origin. We further analyzed tumor-infiltrated DCs. The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), whereas cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating antitumor immune responses in an orthotopic murine lung cancer model.

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

Janibacter alittae sp. nov., an actinobacterium isolated from the gut of marine sandworm (Alitta virens).

A novel Gram-stain-positive, facultatively anaerobic, non-motile, catalase-positive, oxidase-negative and ovoid cocci, designated as A1S7T, was isolated from the gut of a marine sandworm (Alitta virens). Strain A1S7T exhibited optimal growth at temperatures of 20-30 ℃, pH 6-8 and in the presence of 2-4% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain A1S7T belonged to the genus Janibacter, exhibiting a similarity of 99.0% to Janibacter cremeus KCTC 49873T, followed by Janibacter anophelis KCTC 19282T (98.8%), Janibacter hoylei KCTC 49872T (98.4%), Janibacter limosus KACC 20518T (98.2%) and Janibacter corallicola KACC 21120T (97.2%). The complete genome sequence of strain A1S7T revealed a genome size of 3360920 bp with a genomic G+C content of 70.1 mol%. The orthologous average nucleotide identity and the digital DNA-DNA hybridization values between strain A1S7T and Janibacter cremeus KCTC 49873T were determined to be 89.5 and 37.2%, respectively. The major respiratory quinone was MK-8(H4). The predominant fatty acids (>10%) included iso-C16:0, C17:1 ω8c, C18:1 ω9c and C17:0. Polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown phosphoglycolipid and three unknown polar lipids. The cell-wall peptidoglycan type was A1γ. The major whole-cell sugars were ribose, mannose and glucose. Based on phenotypic, phylogenetic, genotypic and chemotaxonomic properties, strain A1S7T represents a novel species in the genus Janibacter, for which the name Janibacter alittae sp. nov. is proposed. The type strain is A1S7T (=KCTC 49714T = JCM 36706T).

Plasma enhanced atomic layer deposition of silicon nitride using magnetized very high frequency plasma.

To obtain high-quality SiNxfilms applicable to an extensive range of processes, such as gate spacers in fin field-effect transistors (FinFETs), the self-aligned quadruple patterning process, etc, a study of plasma with higher plasma density and lower plasma damage is crucial in addition to study on novel precursors for SiNxplasma-enhanced atomic layer deposition (PEALD) processes. In this study, a novel magnetized PEALD process was developed for depositing high-quality SiNxfilms using di(isopropylamino)silane (DIPAS) and magnetized N2plasma at a low substrate temperature of 200 °C. The properties of the deposited SiNxfilms were analyzed and compared with those obtained by the PEALD process using a non-magnetized N2plasma source under the same conditions. The PEALD SiNxfilm, produced using an external magnetic field (ranging from 0 to 100 G) during the plasma exposure step, exhibited a higher growth rate (∼1 Å/cycle) due to the increased plasma density. Additionally, it showed lower surface roughness, higher film density, and enhanced wet etch resistance compared to films deposited using the PEALD process with non-magnetized plasmas. This improvement can be attributed to the higher ion flux and lower ion energy of the magnetized plasma. The electrical characteristics, such as interface trap density and breakdown voltage, were also enhanced when the magnetized plasma was used for the PEALD process. Furthermore, when SiNxfilms were deposited on high-aspect-ratio (30:1) trench patterns using the magnetized PEALD process, an improved step coverage of over 98% was achieved, in contrast to the conformality of SiNxdeposited using non-magnetized plasma. This enhancement is possibly a result of deeper radical penetration enabled by the magnetized plasma.

Pinuseldarone, a Clerodane-Type Diterpene from Pinus eldarica Needles and Phytochemicals as Novel Agents for Regulating Brown Adipogenesis and Thermogenesis.

Phytochemical investigation of the MeOH extract of Pinus eldarica needles led to the isolation and identification of a new clerodane-type diterpene, pinuseldarone (1), along with a known flavonoid, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2), through HPLC purification. The structure of the new compound 1 was elucidated using spectroscopic methods, including 1D and 2D NMR, as well as HRESIMS. Its absolute configuration was established through NOESY analysis and computational methods, including electronic circular dichroism (ECD) calculations and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ probability analysis. The metabolic implications of the isolated compounds were assessed using a cultured brown adipocyte model derived from murine brown adipose tissue. It was observed that treatment with dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2) downregulates the adipogenic marker C/EBPδ and fatty acid transporter CD36, resulting in a significant reduction in lipid accumulation during brown adipocyte differentiation. However, pinuseldarone (1) treatment did not affect brown adipocyte differentiation. Interestingly, pretreatment with pinuseldarone (1) potentiated the pharmacological stimulation of brown adipocytes, seemingly achieved by sensitizing their response to ß3-adrenoreceptor signaling. Therefore, our findings indicate that phytochemicals derived from P. eldarica needles could potentially serve as valuable compounds for adjusting the metabolic activity of brown adipose tissue, a vital component in maintaining whole-body metabolic homeostasis.

Structural Diversification of Pyrazinone Metabolites via Spontaneous Oxa-Michael Addition in Staphylococcus xylosus.

A family of pyrazinone metabolites (1-11) were characterized from Staphylococcus xylosus ATCC 29971. Six of them were hydroxylated or methoxylated, which were proposed to be produced by the rare noncatalytic oxa-Michael addition reaction with a water or methanol molecule. It was confirmed that isopropyl alcohol can also be the Michael donor of the reaction. 1-7 and the synthetic precursor 2a showed significant inhibition of breast cancer cell migration.

The selection of a nitrogen precursor for the construction of N-doped titanium dioxide with enhanced photocatalytic activity for the removal of gaseous toluene.

The preparation of nitrogen-doped TiO2 (i.e., N-TiO2) catalysts is a highly effective option to improve the photocatalytic activity of TiO2. Nonetheless, relatively little is known about the effects of dopant precursors selected for their preparation with regard to the photocatalytic efficacy. In this study, three types of dopants are selected and used as N sources (urea (U), melamine (M), and aqueous ammonia (A)) for N-TiO2 samples with the name codes of NTU, NTM, and NTA, respectively. The photocatalytic efficacy of these N-TiO2 samples is examined against toluene in a packed bed flow reactor. Under optimal conditions (e.g., relative humidity (RH) = 20% and gas hourly space velocity (GHSV) = 1698 h-1), the superiority of NTA is evident over others with a quantum efficiency (QE) of 7.03 × 10-4 molecules photon-1, a space time yield (STY) of 1.38 × 10-4 molecules photon-1 mg-1, and a specific clean air delivery rate (SCADR) of 1148.8 L g-1 h-1. The analysis based on in-situ diffuse reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry confirms the formation of several intermediates such as benzyl alcohol, benzaldehyde, benzoic acid, and alkane species through ring opening reactions. In addition, the prepared NTA photocatalyst exhibits the highest toluene photocatalytic degradation efficiency among all TiO2-based catalysts surveyed to date. Overall, this study offers as a valuable guideline for the development of advanced TiO2 catalytic systems (such as N-TiO2) for the treatment of aromatic hydrocarbons in indoor air.

Low-temperature thermocatalytic removal of formaldehyde in air using copper manganite spinels.

The removal of formaldehyde (FA) is vital for indoor air quality management in light of its carcinogenic propensity and adverse environmental impact. A series of copper manganite spinel structures (e.g., CuMn2O4) are prepared using the sol-gel combustion method and treated with reduction or oxidation pretreatment at 300 °C condition. Accordingly, CuMn2O4-O ("O" suffix for oxidation pre-treatment in air) is identified as the best performer to achieve 100% conversion (XFA) of FA (50 ppm) at 90 °C; its performance, if assessed in terms of reaction kinetic rate (r) at XFA = 10%, is 5.02E-03 mmol g-1 h-1. The FA removal performance increases systematically with decreases in flow rate, FA concentration, and relative humidity (RH) or with increases in bed mass. The reaction pathways and intermediates of FA catalytic oxidation on CuMn2O4-A are studied with density functional theory simulations, temperature-programmed characterization experiments, and in-situ diffuse reflectance infrared Fourier transform spectroscopy. The synergistic combination of large quantities of adsorbed oxygen (OA) species and oxidized metal species (e.g., Cu2+) contribute to the enhanced catalytic performance of CuMn2O4-O to oxidize FA into CO2 with the reaction intermediates of H2CO2 (DOM), HCOO-, and CO. The present study is expected to provide valuable insights into the thermocatalytic oxidation of FA over spinel CuMn2O4 materials and their catalytic performances in relation to the key process variables.

Short-term storability of volatile organic compounds in bag sampling systems under ambient conditions.

Although bag sampling is a common quantification tool for volatile organic compounds (VOCs), it can serve as a major source of experimental bias, when storing even over a short duration (<24 h). To learn more about the reliability of the bag sampling method, the temporal stability of 27 VOCs (classified into five groups (i.e., aldehydes, nonpolar aromatic hydrocarbons, aliphatic carboxylic acids, phenol and methylphenols, and miscellaneous odorants) is assessed using poly-ester aluminum (PEA) bags at five intervals over a day (0.17, 1, 2, 6, and 24 h). In terms of reproducibility (e.g., relative standard error [RSEt, %]), nonpolar aromatic hydrocarbons (BTXS) exhibit the highest consistency (e.g., average RSE <1.55%). Considerable loss of VOCs is observed in the preparation of gaseous standards from a liquid phase standard when assessed by gas/liquid (G/L) ratio. Further, VOCs with lower molecular weights (e.g., propionaldehyde: 77%-94.4%) and branched molecular structures (e.g., isovaleraldehyde: 67.2%-78.9%) tend to have high G/L ratio (e.g., relative to valeraldehyde: 55.1%-66%). The overall relative recovery (RR; %) values of VOCs indicate an exponential decrease over 24 h. BTXS maintain fairly good RR values (above 94.3% at all intervals), possibly due to the nonpolar structure with uniform distribution of π electrons. In contrast, indole and skatole show the least preservation after 24 h (e.g., RR4 values of 10.9% and 24.6%, respectively) due to their highly reactive characteristics. The storability of VOCs appears to be affected by a number of variables (e.g., molecular weight, presence of ethyl branch, and time: e.g., R2 > 0.9). The results of this study offer valuable guidelines for the accurate quantification of VOC levels in air.

Tuning the metal-support interactions in titanium dioxide-supported palladium photocatalysts against toluene in air.

The activity of supported noble metal (e.g., palladium (Pd)) catalysts is often governed by the combined effects of multiple factors (e.g., electronic and geometric properties of the support, surface chemistry of metal nanoparticles (NPs), and metal-support interactions). Pd/titanium dioxide (TiO2) catalyst has been developed as a highly efficient photocatalytic degradation (PCD) system against gaseous toluene based on high-temperature pretreatment (300 and 450 °C) in a mixed stream of hydrogen (H2) and (N2). The interaction of Pd NPs with TiO2 synergistically improves the PCD efficiency of toluene through the efficient adsorption and activation of toluene as well as molecular oxygen (O2) and water (H2O) for the facile generation of reactive oxygen species (ROS (e.g., superoxide anion (•O2-) and hydroxyl (•OH) radicals)). The PCD efficiency of the prepared sample against 5 ppm toluene (at 20% relative humidity (RH)) is 79.6% with the values of maximum reaction rate, quantum yield, space-time yield, and clean air delivery rate as 9.9 µmol g-1 h-1, 1.68E-03 molecules photon-1, 1.68E-02 molecules photon-1 g-1, and 4.8 L h-1, respectively. Based on this research, the PCD mechanism of gaseous toluene has been explored along with the dynamic behavior of O2 and H2O for ROS generation and their relative contribution to the PCD of toluene. As such, this research offers a perspective for designing advanced photocatalysts through surface defect engineering.

Reduced and modified graphene oxide with Ag/V2O5 as a ternary composite visible light photocatalyst against dyes and pesticides.

Water pollution by dyes and pesticides poses significant threats to our ecosystem. In this research, a visible-light ternary composite photocatalytic system was fabricated using graphene oxide (GO) by reducing with N2H4, modifying with KOH, and decorating with Ag/V2O5. The fabricated photocatalysts were characterized through FTIR, SEM, XRD, BET, PL, EDX, ESR, UV-vis spectroscopy, TGA, ESI-MS, and Raman spectroscopy. The point zero charge of the reduced and modified GO (RMGO/Ag/V2O5) was measured to be 6.7 by the pH drift method. This ternary composite was able to achieve complete removal of methyl orange (MO) and chlorpyrifos (CP) in solutions in 80 min under the optimum operation conditions (e.g., in terms of pollutant/catalyst concentrations, pH effects, and contact time). The role of active species responsible for photocatalytic activity was confirmed by scavenger analysis and ESR investigations. The potential mechanism for photocatalytic activity was studied through a fragmentation process carried out by MS analysis. Through nonlinear fitting of the experimental data, MO and CP exhibited the best fit results with the pseudo 1st-order kinetics (quantum yields of 1.07 × 10-3 and 2.16 × 10-3 molecules photon-1 and space-time yields of 1.53 × 10-5 and 2.7 × 10-5 molecules photon-1 mg-1, respectively). The structure of the nanomaterials remained mostly intact to support increased stability and reusability of the prepared photocatalysts even after 10 successive regeneration cycles.

Comparison of Eastern and Western patients undergoing bariatric surgery at two US and Korean institutions: a retrospective analysis of differing bariatric patient populations.

BACKGROUND: Currently, there are differences in both demographics and indications for bariatric surgery between Eastern and Western countries. We compared postoperative outcomes between Korean and American bariatric programs in order to assess how bariatric surgery differently affects these populations. METHODS: We enrolled 540 patients who underwent bariatric surgery at University of California, Los Angeles (UCLA) and 85 patients who underwent surgery at Kosin University Gospel Hospital (KUGH) between January 2019 and December 2020. We compared demographics, complications, weight loss, and metabolic parameters between these groups. RESULTS: There was a difference in age between the UCLA and KUGH patient groups (44.3 years vs 37.6 years, P < 0.01). Frequencies of T2DM and OSA were also different (4.2% vs 50.6%, 34.1% vs 85.9% P < 0.01. Length of hospital stay varied (1.55 days vs 6.68 days, P < 0.01), but there was no difference in operating time and complications. There was no difference in percent of excess weight loss between the two groups at 6 months (29.7 vs 33.8, P = 0.13). Hepatic steatosis index (HSI) was higher in the UCLA group both before (54.2 vs 51.5, P < 0.01) and after (44.4 vs 40.0, P = 0.02) surgery. LSG was the most frequently performed operation, and robotic surgery and revisions were performed only in the UCLA program. CONCLUSION: There were differences in age, BMI, length of stay, and choice of operation between Korean and American bariatric patients. Also, there were differences in the degree of fatty liver disease using HSI and liver enzymes before and after surgery. There was no significant differences in operation time and complications. These findings suggest differences in bariatric practices and reactions to bariatric surgery in Eastern and Western settings.

CX3CR1+ Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26.

Rationale: The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated. Objectives: Our objectives were to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation. Methods: For the study, we used the institutional review board-approved protocol for human subsegmental bronchoprovocation with allergen, mouse models for allergic lung inflammation, and novel transgenic mice, including a conditional CCL26 knockout. The samples were analyzed using mass cytometry, single-cell RNA sequencing, and biophysical and immunological analyses. Measurements and Main Results: We compared alveolar macrophage (AM) subsets in the BAL before and after allergen provocation. In response to provocation with inhaled allergens, the subsets of AMs are dynamically changed in humans and mice. In the steady state, the AM subset expressing CX3CR1 is a relatively small fraction in bronchoalveolar space and lung tissue but drastically increases after allergen challenges. This subset presents unique patterns of gene expression compared with classical AMs, expressing high C1q family genes. CX3CR1+ macrophages are activated by airway epithelial cell-derived CCL26 via a receptor-ligand interaction. The binding of CCL26 to the CX3CR1+ receptor induces CX3CR1+ macrophages to secrete C1q, subsequently facilitating the clearance of eosinophils. Furthermore, the depletion of CX3CR1 macrophages or CCL26 in airway epithelial cells delays the resolution of allergic lung inflammation displaying prolonged tissue eosinophilia. Conclusions: These findings indicate that the CCL26-CX3CR1 pathway is pivotal in resolving eosinophilic allergic lung inflammation.

Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors.

INTRODUCTION: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. METHODS: Using the 2014-2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. RESULTS: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). CONCLUSIONS: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.

Development of a FRET aptasensor based on MoS2-doped Zn-MOF as luminophore for selective detection of cadmium in aqueous solutions.

A robust "on-off" fluorescent aptasensor was developed using nanohybrids of molybdenum sulfide (MoS2) quantum dot (QD)-doped zinc metal-organic frameworks (Zn-MOF) for selective and sensitive detection of cadmium ions (Cd2+) in water. This nanohybrid (MoS2@Zn-MOF), synthesized via "bottle around the ship" methodology, exhibited a high-intensity fluorescence emission centered at 430 nm (λEm) (blue) on excitation at 320 nm (λEx). Further, the conjugation of this fluorophore to phosphate-modified cadmium aptamer (Cd-2-2) was achieved through carbodiimide reaction. The hybridization of prepared sensing probe (MoS2@Zn-MOF/Cd-2-2 aptamer) was done with dabcyl-conjugated complementary DNA (cDNA), acting as energy donor-acceptor pair in the fluorescence resonance energy transfer (FRET) system. This hybridization causes the fluorescence quenching of the nanohybrid. In the presence of Cd2+, the aptamer from the fabricated nano-biosensing probe binds to these ions, resulting in release of dabcyl-cDNA oligomer. This release of dabcyl-cDNA oligomer from the sensing probes restores the fluorescence of the nanohybrid. Under optimized conditions (sensing probe/dabcyl-cDNA ratio 1/7, pH 7.4, and temp 28 °C), the sensing probe showed a fast response time of 1 min. The fluorescence intensity of the nanohybrid can be utilized to determine the concentration of Cd2+. The proposed aptasensor achieved highly sensitive detection of Cd2+ with a limit of detection (LOD) of 0.24 ppb over the range of 1 × 10-9 to 1 × 10-4 M along with minimal effects of interferences (e.g., Hg2+, Pb2+, and Zn2+) and good reproducibility. The designed aptasensor based on MoS2@Zn-MOF nanofluorophore offers a highly sensitive and selective approach for rapid screening of metal ions in aqueous environments.

Complement C1q essential for aeroallergen sensitization via CSF1R+ conventional dendritic cells type 2.

BACKGROUND: Dendritic cells (DCs) are heterogeneous, comprising multiple subsets with unique functional specifications. Our previous work has demonstrated that the specific conventional type 2 DC subset, CSF1R+cDC2s, plays a critical role in sensing aeroallergens. OBJECTIVE: It remains to be understood how CSF1R+cDC2s recognize inhaled allergens. We sought to elucidate the transcriptomic programs and receptor-ligand interactions essential for function of this subset in allergen sensitization. METHODS: We applied single-cell RNA sequencing to mouse lung DCs. Conventional DC-selective knockout mouse models were employed, and mice were subjected to inhaled allergen sensitization with multiple readouts of asthma pathology. Under the clinical arm of this work, human lung transcriptomic data were integrated with mouse data, and bronchoalveolar lavage (BAL) specimens were collected from subjects undergoing allergen provocation, with samples assayed for C1q. RESULTS: We found that C1q is selectively enriched in lung CSF1R+cDC2s, but not in other lung cDC2 or cDC1 subsets. Depletion of C1q in conventional DCs significantly attenuates allergen sensing and features of asthma. Additionally, we found that C1q binds directly to human dust mite allergen, and the C1q receptor CD91 (LRP1) is required for lung CSF1R+cDC2s to recognize the C1q-allergen complex and induce allergic lung inflammation. Lastly, C1q is enriched in human BAL samples following subsegmental allergen challenge, and human RNA sequencing data demonstrate close homology between lung IGSF21+DCs and mouse CSF1R+cDC2s. CONCLUSIONS: C1q is secreted from the CSF1R+cDC2 subset among conventional DCs. Our data indicate that the C1q-LRP1 axis represents a candidate for translational therapeutics in the prevention and suppression of allergic lung inflammation.

Comparative Analysis of Temperature-Responsive Hydrogel (PF 72) for Postoperative Pain After Bimaxillary Surgery: A Retro-spective Study.

Bimaxillary surgery is a painful invasive procedure in plastic surgery. Pain control is typically achieved using intravenous analgesics. We aimed to investigate the efficacy of a novel temperature-responsive hydrogel, PF72, mixed with ropivacaine, as a local pain management solution when applied directly to the surgical site following orthognathic surgery. The study was conducted from October 2022 to July 2023 and included a cohort of 40 candidates for orthognathic surgery, encompassing LeFort I maxillary ostectomy and sagittal split ramus osteotomy. The participants were divided into an Injection group (n = 20), where PF72 was administered at the surgical site before the orthognathic surgery, and a Control group (n = 20), which relied solely on intravenous analgesics. Pain was evaluated at 3, 6, 24, 48, and 72 h after surgery using a numerical rating scale (NRS). The mean NRS scores at 24 h were 6.35 and 4 for the Control and Injection groups, respectively. The mean NRS scores at 72 h were 3.4 and 2.55 for the Control and Injection groups, respectively. Patients who received PF72 experienced less pain than those who received intravenous analgesics. These findings underscore the potential of PF72 as an effective alternative for enhancing pain management in patients undergoing orthognathic surgery.Level of Evidence III Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .