iSERS: from nanotag design to protein assays and ex vivo imaging.

Proteins are an eminently important class of ubiquitous biomacromolecules with diverse biological functions, and numerous techniques for their detection, quantification, and localisation have been developed. Many of these methods exploit the selectivity arising from molecular recognition of proteins/antigens by immunoglobulins. The combination of surface-enhanced Raman scattering (SERS) with such "immuno"-techniques to immuno-SERS (iSERS) is the central topic of this review, which is focused on colloidal SERS nanotags, i.e., molecularly functionalised noble metal nanoparticles conjugated to antibodies, for their use in protein assays and ex vivo imaging. After contrasting the fundamental differences between label-free SERS and iSERS, including a balanced description of the advantages and drawbacks of the latter, we describe the usual workflow of iSERS experiments. Milestones in the development of the iSERS technology are summarised from a historical perspective. By highlighting selected examples from the literature, we illustrate the conceptual progress that has been achieved in the fields of iSERS-based protein assays and ex vivo imaging. Finally, we attempt to predict what is necessary to fully exploit the transformative potential of the iSERS technology by stimulating the transition from research in academic labs into applications for the benefit of our society.

Spectroscopic Identification of Charge Transfer of Thiolated Molecules on Gold Nanoparticles via Gold Nanoclusters.

Investigation of charge transfer needs analytical tools that could reveal this phenomenon, and enables understanding of its effect at the molecular level. Here, we show how the combination of using gold nanoclusters (AuNCs) and different spectroscopic techniques could be employed to investigate the charge transfer of thiolated molecules on gold nanoparticles (AuNP@Mol). It was found that the charge transfer effect in the thiolated molecule could be affected by AuNCs, evidenced by the amplification of surface-enhanced Raman scattering (SERS) signal of the molecule and changes in fluorescence lifetime of AuNCs. Density functional theory (DFT) calculations further revealed that AuNCs could amplify the charge transfer process at the molecular level by pumping electrons to the surface of AuNPs. Finite element method (FEM) simulations also showed that the electromagnetic enhancement mechanism along with chemical enhancement determines the SERS improvement in the thiolated molecule. This study provides a mechanistic insight into the investigation of charge transfer at the molecular level between organic and inorganic compounds, which is of great importance in designing new nanocomposite systems. Additionally, this work demonstrates the potential of SERS as a powerful analytical tool that could be used in nanochemistry, material science, energy, and biomedical fields.

Mn2+-Triggered Swing-Arm Robot Strategy Using Anemone-Like Thi@AuPd@Cu-MOFs as Signaling Probes for the Detection of T-2 Toxin.

Herein, we synthesized anemone-like copper-based metal-organic frameworks (MOFs) loaded with gold-palladium nanoparticles (AuPd@Cu-MOFs) and polyethylenimine-reduced graphene oxide/gold-silver nanosheet composites (PEI-rGO/AuAg NSs) for the first time to construct the sensor and to detect T-2 toxin (T-2) using triple helix molecular switch (THMS) and signal amplification by swing-arm robot. The aptasensor used PEI-rGO/hexagonal AuAg NSs as the electrode modification materials and anemone-like AuPd@Cu-MOFs as the signal materials. The prepared PEI-rGO/hexagonal AuAg NSs had a large specific surface area, excellent electrical conductivity, and good stability, which successfully improved the electrochemical performance of the sensors. The AuPd@Cu-MOFs with high porosity provided a great deal of attachment sites for the signaling molecule thionine (Thi), thereby increasing the signal response. The aptasensor developed in this study demonstrated a remarkable detection limit of 0.054 fg mL-1 under optimized conditions. Furthermore, the successful detection of T-2 in real samples was achieved using the fabricated sensor. The simplicity of the THMS-based method, which entails modifying the aptamer sequence, allows for easy adaptation to different target analytes. Thus, the sensor holds immense potential for applications in quality supervision and food safety.

Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study.

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.

Feeding artery: a valuable feature for differentiation of regenerative nodule, dysplastic nodules and small hepatocellular carcinoma in CEUS LI-RADS.

OBJECTIVE: To investigate whether the feeding artery (FA) feature can aid in discriminating small hepatocellular carcinoma (HCC) using the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) from precancerous lesions. METHODS: Between June 2017 and May 2021, a total of 347 patients with 351 precancerous liver lesions or small HCCs who underwent CEUS were enrolled. Two independent radiologists assigned LI-RADS categories to all lesions and assessed the presence of the FA feature, which was used as an ancillary feature to either upgrade or downgrade the LI-RADS category. The diagnostic performance of CEUS LI-RADS, both with and without the FA feature, was evaluated based on accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The FA feature was found to be more prevalent in HCC (85.54%, p < 0.001) than in regenerative nodules (RNs, 29.73%), low-grade dysplastic nodules (LGDNs, 33.33%), and high-grade dysplastic nodules (HGDNs, 55.26%). Furthermore, the presence of arterial phase hyperenhancement (APHE), washout (WO), and FA in liver nodules was associated with a higher expression of GPC-3 and Ki-67 compared to the group without these features (p < 0.001). After adjusting, the sensitivity and accuracy of LR-5 for HCC improved from 68.67% (95%CI: 62.46%, 74.30%) to 77.51% (95%CI: 71.72%, 82.44%) and from 69.23% (95%CI: 64.11%, 74.02%) to 73.79% (95%CI: 68.86%, 78.31%), respectively. CONCLUSION: The FA feature is a valuable feature for distinguishing small HCC and precancerous lesions and could be added as a possible ancillary feature in CEUS LI-RADS which was backed up by biomarkers. CLINICAL RELEVANCE STATEMENT: The presence of a feeding artery is a valuable imaging feature in the differentiation of HCC and precancerous lesions. Incorporating this characteristic in the CEUS LI-RADS can enhance the diagnostic ability. KEY POINTS: • Feeding artery is more frequent in HCC than in regenerative nodules, low-grade dysplastic nodules, and high-grade dysplastic nodules. • Feeding artery feature is a valuable ancillary feature for CEUS LI-RADS to differentiate regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, and HCC. • The existence of feeding artery, arterial phase hyperenhancement, and washout is associated with more GPC-3 positive expression and higher Ki-67 expression than the group without these features.

Multiplex detection of bacterial pathogens by PCR/SERS assay.

Bacterial infections are a leading cause of death globally. The detection of DNA sequences correlated to the causative pathogen has become a vital tool in medical diagnostics. In practice, PCR-based assays for the simultaneous detection of multiple pathogens currently rely on probe-based quantitative strategies that require expensive equipment but have limited sensitivity or multiplexing capabilities. Hence, novel approaches to address the limitations of the current gold standard methods are still in high demand. In this study, we propose a simple multiplex PCR/SERS assay for the simultaneous detection of four bacterial pathogens, namely P. aeruginosa, S. aureus, S. epidermidis, and M. smegmatis. Wherein, specific primers for amplifying each target gDNA were applied, followed by applying SERS nanotags functionalized with complementary DNA probes and Raman reporters for specific identification of the target bacterial pathogens. The PCR/SERS assay showed high specificity and sensitivity for genotyping bacterial pathogen gDNA, whereby as few as 100 copies of the target gDNA could be detected. With high sensitivity and the convenience of standard PCR amplification, the proposed assay shows great potential for the sensitive detection of multiple pathogen infections to aid clinical decision-making.

Lectin-conjugated nanotags with high SERS stability: selective probes for glycans.

Surface-enhanced Raman scattering (SERS) nanotags functionalized with lectins as the biological recognition element can be used to target the carbohydrate portion of carbohydrate-carrying molecules (glycoconjugates). An investigation of the optical stability of such functionalized SERS nanotags is an essential initial step before future application and quantification of surface glycan biomarkers on cells and extracellular vesicles. Herein, we report an innovative approach to evaluate the SERS stability of lectin-conjugated nanotags by investigating any possible interfering lectin-lectin interactions in a mixture of different lectin-conjugated SERS nanotags, as well as an assessment of lectin-glycan interaction by mixing wheat germ agglutinin (WGA)-conjugated SERS nanotags with different glycoproteins. No lectin cross-reactivity was found in the mixture of lectin-conjugated SERS nanotags, evidenced by the constant SERS intensity. Additionally, the results showed that the lectins conjugated to SERS nanotags retain their ability to interact with glycans, as evidenced by the changes in the nanotag color and extinction spectra. Their SERS intensity remained constant as supported by finite-element method (FEM) simulation results, demonstrating a high SERS stability and selectivity of lectin-conjugated nanotags towards multiplex applications.

Metal-Organic Framework Featuring Cubic Caged Structures for One-Step Ethylene Purification from Ethylene/Ethane Mixtures.

Separation of C2H6/C2H4 mixtures is of significant importance in the chemical industry but remains a challenge due to the physicochemical similarities of C2H6 and C2H4. Herein, a metal-organic framework (MOF), [Zn4(µ4-O)(PCTF)3]n (Zn-PCTF) (PCTF2-= 5-trifluoromethyl-1H-pyrazole-4-carboxylic), is provided for the removal of C2H6 from C2H6/C2H4 mixtures. Zn-PCTF displays a three-dimensional framework featuring one-dimensional pore channels with periodic bottleneck segments. The well-balanced C2H6 adsorption capacity (79.0 cm3 g-1 at 298 K) and C2H6/C2H4 selectivity (1.8) for Zn-PCTF under ambient conditions boost Zn-PCTF with highly promising potentials for efficient purification of C2H4 from C2H6/C2H4 mixtures, which is verified by the dynamic column breakthrough experiments. The well-matched caged pores and suitable pore chemistry (particularly the presence of abundant Lewis base sites (N, O, and F) on the pore surfaces) for C2H6 account for the high-performance C2H6/C2H4 separation of Zn-PCTF unveiled by computational simulations.

Metal-Organic Frameworks Possessing Suitable Pores for Xe/Kr Separation.

Adsorption separation of the Xe/Kr mixture remains a tough issue since Xe and Kr have an inert nature and similar sizes. Here we present a chlorinated metal-organic framework (MOF) [JXNU-19(Cl)] and its nonchlorinated analogue (JXNU-19) for Xe/Kr separation. The two isostructural MOFs constructed from the heptanuclear cobalt-hydroxyl clusters bridged by organic ligands are three-dimensional structures. Detailed contrast of the Xe/Kr adsorption separation properties of the MOF shows that significantly enhanced Xe uptakes and Xe/Kr adsorption selectivity (17.1) are observed for JXNU-19 as compared to JXNU-19(Cl). The main binding sites for Xe in the MOF revealed by computational simulations are far away from the chlorine sites, suggesting that the introduction of the chlorine groups results in the unfavorable Xe adsorption for JXNU-19(Cl). The optimal pores, high surface area, and multiple strong Xe-framework interactions facilitate the effective Xe/Kr separation for JXNU-19.

Near-full-length genome analysis of two novel HIV second recombinant forms in Hebei, China.

The number of individuals infected with HIV-1 among men who have sex with men (MSM) has risen rapidly in recent years in China, and the subtypes CRF01_AE, CRF07_BC, and B, as well as many novel unique recombinant forms (URFs) are prevalent among them. Co-circulation of strains among MSM populations allows the generation of circulating recombinant forms (CRFs) and URFs. In this study, we identified two new URFs from two HIV-1-positive subjects who were infected through homosexual contact in Hebei, China. Analysis of near-full-length genome sequences, using phylogenetic and recombination analysis showed that the two URFs originated from CRF01_AE, CRF07_BC, and B, and CRF01_AE segments in the backbone of the URFs were derived from cluster 4 of CRF01_AE. The CRF07_BC segments of two URFs were clustered with 07BC_N in a phylogenetic tree. The identification of novel URFs with complex genomic structures shows that it is necessary to strengthen surveillance of HIV-1 variants in MSM populations in this region.

Etching of Ag nanoparticles triggered bidirectional regulation for electrochemiluminescence ratiometric immunoassay.

A highly efficient ratiometric electrochemiluminescence (ECL) immunoassay was explored by bidirectionally regulating the ECL intensity of two luminophors. The immunoassay was conducted in a split-type mode consisting of an ECL detection procedure and a sandwich immunoreaction. The ECL detection was executed using a dual-disk glassy carbon electrode modified with two potential-resolved luminophors (g-C3N4-Ag and Ru-MOF-Ag nanocomposites), and the sandwich immunoreaction using glucose oxidase (GOx)-modified SiO2 nanospheres as labels was carried out in a 96-well plate. The Ag nanoparticles (NPs) acted as bifunctional units both for triggering the resonance energy transfer (RET) with g-C3N4 and for accelerating the electron transfer rate of the Ru-MOF-Ag ECL reaction. When the H2O2 catalyzed by GOx in the 96-well plate was transferred to the dual-disk glass carbon electrode, the doped Ag NPs in the two luminophors could be etched, thus destroying the RET between C3N4 and the accelerated reaction to Ru-MOF, resulting in an opposite trend in the ECL signal outputted from the dual disks. Using the ratio of the two signals for quantification, the constructed immunosensor for a model target, i.e. myoglobin, exhibited a low detection limit of 4.7 × 10-14 g/mL. The ingenious combination of ECL ratiometry, bifunctional Ag NPs, and a split-type strategy effectively reduces environmental and human errors, offering a more precise and sensitive analysis for complex samples.

Enhanced stability of CsPbBr3 nanocrystals through Al2O3 and polymer coating.

Lead halide perovskite nanocrystals have emerged as a promising candidate for next-generation display applications due to their attractive optical properties and low-cost production. However, the environmental stability of perovskite remains a major challenge, hindering their practical applications and scalability for commercialization. In this study, we present an effective method to enhance the stability of CsPbBr3 nanocrystals by coating them with a combination of Al2O3 and a polymer. The unique double protection structure significantly improves their resistance to moisture, heat, and polar solvents. It is worth noting that compared with the ordinary CsPbBr3 nanocrystals, the modified nanocrystals have better stability and higher luminous intensity. After soaking in water for 360 hours, the modified nanocrystals retained 85% of their initial luminous intensity. Under optimal conditions, the luminous intensity of modified nanocrystals increased by 36%. Furthermore, the thermal stability and organic solvent resistance of the nanocrystals are improved compared with the nanocrystals uncoated with Al2O3. The synthesized white light emitting diode using the modified PNCs achieves a color gamut coverage rate of 129% under standard NTSC, and 95% under standard Rec.2020, indicating its potential for future display applications. This research presents a promising approach for the development of stable perovskite nanocrystals with enhanced performance in various optoelectronic devices.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Correlation Analysis of Multi-Scale Ictal EEG Signals in Juvenile Myoclonic Epilepsy.

BACKGROUND: To explore the time-frequency structure and cross-scale coupling of electroencephalography (EEG) signals during seizure in juvenile myoclonic epilepsy (JME), correlations between different leads, as well as dynamic evolution in epileptic discharge, progression and end of seizure were examined. METHODS: EEG data were obtained for 10 subjects with JME and 10 normal controls and were decomposed using gauss continuous wavelet transform (CWT). The phase amplitude coupling (PAC) relationship between the 11th (4.57 Hz) and 17th (0.4 Hz) scale was investigated. Correlations were examined between the 11th and 17th scale EEG signals in different leads during seizure, using multi-scale cross correlation analysis. RESULTS: The time-frequency structure of JME subjects showed strong rhythmic activity in the 11th and 17th scales and a close PAC was identified. Correlation analysis revealed that the ictal JME correlation first increased in the anterior head early in seizure and gradually expanded to the posterior head. CONCLUSION: PAC was exhibited between the 11th and 17th scales during JME seizure. The results revealed that the correlation in the anterior leads was higher than the posterior leads. In the perictal period, the 17th scale EEG signal preceded the 11th scale signal and remained for some time after a seizure. This suggests that the 17th scale signal may play an important role in JME seizure.

Free vascularized bone graft from the lateral epicondylar region of the humerus for treatment of scaphoid nonunion.

BACKGROUND: Free vascularized bone grafting (FVBG) has become one of the essential methods for treating scaphoid nonunion complicated by avascular necrosis. However, commonly used bone graft, including the medial femoral condyle bone graft and iliac crest bone graft, still present challenges such as a high rate of donor site complications and variations of vascular pedicle. In this study, we have introduced a novel bone graft-the lateral humeral condyle bone graft with the posterior branch of the radial collateral artery (PBRCA) as the vascular pedicle-as an alternative option, with the aim of overcoming some of the limitations of previously described FVBG procedures. METHODS: Nine patients who had a nonunion of the scaphoid that had been present for an average of 16.8 months (range 9-35 months) were managed with use of a free vascularized bone graft obtained from the lateral humeral epicondylar region. Avascularity of the scaphoid, as assessed on preoperative magnetic resonance imaging and intraoperative bone marrow puncture test. Postoperatively, regular X-ray and CT scans examinations were conducted to assess the progress of fracture healing. Active motion of the wrist, and grip strength recovery were measured periodically. Wrist pain was graded using the Visual Analogue Scale (VAS), while wrist joint functionality was evaluated using the Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) questionnaire and the Patient-Rated Wrist Evaluation (PRWE) scale. The elbow functional outcome was evaluated by the Mayo Elbow Performance Score (MEPS). RESULTS: All of nine lateral humeral epicondylar bone grafts were successfully harvested. The blood supply of the graft during surgery was excellent in six cases and good in three cases. The size of the bone grafts ranges from 1.0 cm × 0.5 cm × 0.5 cm to 2.0 cm × 1.0 cm × 0.5 cm. The average vascular pedicle length was 3.4 cm (range 2.0-6.0 cm). There were no early complications in either the donor or recipient areas after surgery. Union was successfully achieved in all nine patients, with an average time to union of 14.3 weeks (range 11-20 weeks) after surgery. The average follow-up period was 31.2 months (range 26-40 months). At the final follow-up, the average palmar flexion, dorsal extension, radial deviation, and ulnar deviation angles of the injured wrist joint were 56.1° (range 45°-70°), 56.1° (range 40°-80°), 10.6° (range 5°-20°), and 22.2° (range 15°-35°), respectively, which reached 79.0%, 82.1%, 59.4%, and 72.8% of the average activity of the contralateral normal side. The average grip strength of the injured side was 35.2 kg (range 22-51 kg), which was equivalent to 81.3% of the average grip strength of the contralateral side. The average VAS score for wrist joint pain was 1.0 point (range 0-2 points); the Quick-DASH score was 9.2 points (range 6-18 points); and the PRWE score was 13.1 points (range 9-16 points), the Mayo Elbow Performance Index was 100 points (range 100-100 points). One patient reported a feeling of friction during movement but no pain. One patient reported numbness in the donor site. One patient complained of pain when applying force to the scar in the donor area. During the follow-up period, these complications showed improvement without any treatment. CONCLUSION: The FVBG technique has been considered an effective method for treating scaphoid nonunion with avascular necrosis. Compared to traditional FVBG, the lateral humeral epicondylar bone graft exhibits a higher union rate, fewer complications, and easier accessibility, making it a favorable choice.

Timing Matters: A Longitudinal Study Examining the Effects of Physical Activity Intensity and Timing on Adolescents' Mental Health Outcomes.

Physical activity is universally acknowledged for its benefits to mental health; however, the specific intensities and timings that best benefit adolescents' mental health, crucial due to their significant influence on daily schedules, have not been thoroughly investigated. This study addresses the substantive research gap by exploring the varied effects of physical activity intensity (light versus moderate to vigorous) and timing (weekdays versus weekends and holidays) on adolescent mental health. Utilizing a large-scale longitudinal dataset (NT1 = 84,054; NT2 = 44,623) from 158 schools, this research describes the current state of adolescent physical activity and investigates the effects of physical activity on mental health outcomes, including positive (i.e., life satisfaction, positive mental health) and negative indicators (depression, anxiety), over a 6-month period. Participants were adolescents aged 9-19 years (mean age = 12.73 ± 2.43 years, 48.9% female), with the analysis adjusted for potential confounding factors. Results showed that as adolescents grow older, their engagement in moderate-to-vigorous physical activity during both weekdays and weekends/holidays tends to decrease, while light physical activity during weekdays increases. Multilevel regression analysis indicated that moderate-to-vigorous physical activity during weekends/holidays at Time 1 positively correlated with better mental health outcomes at Time 2 (six months later), featuring enhanced positive indicators and reduced negative ones. Moderate-to-vigorous physical activity on weekdays at Time 1 was positively linked to mental health at Time 2. Light physical activity during weekends/holidays at Time 1 positively predicted life satisfaction and positive mental health at Time 2. In contrast, light physical activity on weekdays at Time 1 negatively correlated with life satisfaction at Time 2. The study underscores the importance of promoting moderate-to-vigorous physical activity, particularly on weekends and holidays, to improve mental health outcomes among adolescents.

Cascaded *CO-*COH Intermediates on a Nonmetallic Plasmonic Photocatalyst for CO2-to-C2H6 with 90.6 % Selectivity.

Oxygen vacancies (OV) in nonmetallic plasmonic photocatalysts can decrease the energy barrier for CO2 reduction, boosting C1 intermediate production for potential C2 formation. However, their susceptibility to oxidation weakens C1 intermediate adsorption. Herein we proposed a "photoelectron injection" strategy to safeguard OV in W18O49 by creating a W18O49/ZIS (W/Z) plasmonic photocatalyst. Moreover, photoelectrons contribute to the local multi-electron environment of W18O49, enhancing the intrinsic excitation of its hot electrons with extended lifetimes, as confirmed by in situ XPS and femtosecond transient absorption analysis. Density functional theory calculations revealed that W/Z with OV enhances CO2 adsorption, activating *CO production, while reducing the energy barrier for *COH production (0.054 eV) and subsequent *CO-*COH coupling (0.574 eV). Successive hydrogenation revealed that the free energy for *CH2CH2 hydrogenation (0.108 eV) was lower than that for *CH2CH2 desorption for C2H4 production (0.277 eV), favouring C2H6 production. Consequently, W/Z achieves an efficient C2H6 activity of 653.6 µmol g-1 h-1 under visible light, with an exceptionally high selectivity of 90.6 %. This work offers a new strategy for the rational design of plasmonic photocatalysts with high selectivity for C2+ products.

CD226 knockout reduces the development of CD8+ T by impairing the TCR sensitivity of double-positive thymocytes.

The costimulation molecule CD226 is widely involved in T cell differentiation, activation and immune functional regulation in peripheral immune tissues. CD226-deficient mice have impaired immune response capacity. The function of CD226 in regulating T cell development in the thymus, a central immune organ, is not yet fully understood. We investigated the development of thymocytes using CD226 knockout mice and single-cell sequencing techniques. CD226 began to be expressed in the second half of thymocyte development, with a gradual increase from the double-positive (DP) to single-positive (SP) phase and higher levels of CD226 on CD8+ T cells than on CD4+ T cells from the SP phase to mature T cells. In the thymus of CD226KO mice, the proportion of DPT at the quiescent phase (DPT-Q) increased, of which the Gzma+ cluster that tends to be CD8+ T cells and CD5+ cluster that is undergoing positive selection decreased dramatically. Afterward, the proportion of mature CD8+ T cells reduced dramatically. Depletion of CD226 impaired TCR activation signalling and diminished AKT/ERK/NF-κB/p38 phosphorylation levels. The diminished TCR responsiveness of DPT cells impeded their positive selection process and influenced the maturation of CD8+ T cells. In mechanism, CD226 knockout enhanced DPT cell apoptosis via impairing AKT phosphorylation. These results suggest that CD226 plays a significant role in T cell thymic development via modulation of TCR signalling, affecting CD8+ T cell maturation.

CD226 deficiency exacerbated intestinal immune dysregulation in mice with dinitrochlorobenzene-induced atopic dermatitis.

Intestinal mucosal immunity plays a pivotal role in host defence. In this study, we found that cluster of differentiation 226 (CD226) gene knockout (KO) led to more severe atopic dermatitis (AD)-related skin pathologies and bowel abnormalities in a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model. Following DNCB administration, the expression of CD226 was elevated in intestinal mucosal tissues, including group 3 innate lymphoid cells (ILC3s) and CD4+ T cells of Peyer's patches (PPs). CD226 deficiency led to an overactive intestinal immune response in the AD-like mice, as evidenced by increased inflammation and Th1/Th2-related cytokine levels as well as increased Paneth cell numbers and antimicrobial peptide (AMP) expression, which was likely due to the higher interleukin (IL)-22 production in the lamina propria. Additionally, CD226 deficiency increased the production of IL-4 and IL-17 in mesenteric lymph nodes as well as the number of PPs and expression of immunoglobulin (Ig) A in B cells. Moreover, insufficient expression of CD226 affected the characterization of intraepithelial and lamina propria lymphocytes in the intestinal mucosa. Finally, the number of PPs was increased in CD4+ T cell-specific CD226 KO and regulatory T (Treg) cell-specific CD226 KO mice; thus, loss of CD226 in Treg cells resulted in impaired Treg cell-suppressive function. Therefore, our findings indicate that CD226 deficiency alters intestinal immune functionality in inflammatory diseases.

Mapping and Functional Analysis of QTL for Kernel Number per Row in Tropical and Temperate-Tropical Introgression Lines of Maize (Zea mays L.).

Kernel number per row (KNR) is an essential component of maize (Zea mays L.) grain yield (GY), and understanding its genetic mechanism is crucial to improve GY. In this study, two F7 recombinant inbred line (RIL) populations were created using a temperate-tropical introgression line TML418 and a tropical inbred line CML312 as female parents and a backbone maize inbred line Ye107 as the common male parent. Bi-parental quantitative trait locus (QTL) mapping and genome-wide association analysis (GWAS) were then performed on 399 lines of the two maize RIL populations for KNR in two different environments using 4118 validated single nucleotide polymorphism (SNP) markers. This study aimed to: (1) detect molecular markers and/or the genomic regions associated with KNR; (2) identify the candidate genes controlling KNR; and (3) analyze whether the candidate genes are useful in improving GY. The authors reported a total of 7 QTLs tightly linked to KNR through bi-parental QTL mapping and identified 21 SNPs significantly associated with KNR through GWAS. Among these, a highly confident locus qKNR7-1 was detected at two locations, Dehong and Baoshan, with both mapping approaches. At this locus, three novel candidate genes (Zm00001d022202, Zm00001d022168, Zm00001d022169) were identified to be associated with KNR. These candidate genes were primarily involved in the processes related to compound metabolism, biosynthesis, protein modification, degradation, and denaturation, all of which were related to the inflorescence development affecting KNR. These three candidate genes were not reported previously and are considered new candidate genes for KNR. The progeny of the hybrid Ye107 × TML418 exhibited strong heterosis for KNR, which the authors believe might be related to qKNR7-1. This study provides a theoretical foundation for future research on the genetic mechanism underlying KNR in maize and the use of heterotic patterns to develop high-yielding hybrids.