Offspring nursing extends mother's longevity in a long-term maternal cared spider.

Females typically outlive males in animals, especially in species that provide long-term maternal care. However, life history theory predicts that investments in reproduction, such as lactation and offspring nursing, often shorten caretakers' longevity. Aiming to interpret this paradox, we selected the lactating jumping spider Toxeus magnus to investigate the effects of reproductive activities on longevity for two sexes. We found that: (1) although "milk" provisioning reduces female's longevity, mothers who cared for offspring (provisioned "milk" and nursing) lived the longest compared to virgins and those did not provide care; (2) copulation increased female's longevity but had no effects on males; and (3) the two sexes have comparable developmental duration, but the female adult's longevity was 2.1 times that of male's. This study suggests that the time requirement for offspring dispersal might act as a key selective force favoring females' adulthood extension, which ultimately generates the longer-lived females in maternal cared species.

Silicon photocathode functionalized with osmium complex catalyst for selective catalytic conversion of CO2 to methane.

Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s-1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching -14.11 mA cm-2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.

Leaf isotopes reveal tree diversity effects on the functional responses to the pan-European 2018 summer drought.

Recent droughts have strongly impacted forest ecosystems and are projected to increase in frequency, intensity, and duration in the future together with continued warming. While evidence suggests that tree diversity can regulate drought impacts in natural forests, few studies examine whether mixed tree plantations are more resistant to the impacts of severe droughts. Using natural variations in leaf carbon (C) and nitrogen (N) isotopic ratios, that is δ13C and δ15N, as proxies for drought response, we analyzed the effects of tree species richness on the functional responses of tree plantations to the pan-European 2018 summer drought in seven European tree diversity experiments. We found that leaf δ13C decreased with increasing tree species richness, indicating less drought stress. This effect was not related to drought intensity, nor desiccation tolerance of the tree species. Leaf δ15N increased with drought intensity, indicating a shift toward more open N cycling as water availability diminishes. Additionally, drought intensity was observed to alter the influence of tree species richness on leaf δ15N from weakly negative under low drought intensity to weakly positive under high drought intensity. Overall, our findings suggest that dual leaf isotope analysis helps understand the interaction between drought, nutrients, and species richness.

Integrated Solution for As(III) Contamination in Water Based on Crystalline Porous Organic Salts.

A stable crystalline organic porous salt (CPOSs-NXU-1) with 1D apertures has been assembled by the solvothermal method, which shows high-sensitivity "turn-on" fluorescence detection and large-capacity adsorption of As(III) ions in water. The detection limits, saturated adsorption capacity, and removal rate of CPOSs-NXU-1 for As(III) ions in an aqueous solution can reach 74.34 nm (5.57 ppb), 451.01 mg g-1, and 99.6%, respectively, at pH = 7 and room temperature. With the aid of XPS, IR, Raman, and DFT theoretical calculations, it is determined that CPOSs-NXU-1 adsorbed As(III) ions in the form of H2AsO3 - and H3AsO3 through hydrogen bonding between the host and guest. The mechanism for fluorescence sensitization of As(III) ions to CPOSs-NXU-1 is mainly to increase the energy level difference between the ground state and excited state investigated by UV-vis absorption spectra, UV-vis diffuse reflectance spectra, and theoretical calculations. By constructing fluorescent CPOSs, an integrated solution has been achieved to treating As(III) contamination in the water that is equipped with detection and removal. These results blaze a promising path for addressing trivalent arsenic contamination in water efficiently, rapidly, and economically.

Novel Environmentally Friendly RNAi Biopesticides: Targeting V-ATPase in Holotrichia parallela Larvae Using Layered Double Hydroxide Nanocomplexes.

RNA interference (RNAi)-based biopesticides offer an attractive avenue for pest control. Previous studies revealed high RNAi sensitivity in Holotrichia parallela larvae, showcasing its potential for grub control. In this study, we aimed to develop an environmentally friendly RNAi method for H. parallela larvae. The double-stranded RNA (dsRNA) of the V-ATPase-a gene (HpVAA) was loaded onto layered double hydroxide (LDH). The dsRNA/LDH nanocomplex exhibited increased environmental stability, and we investigated the absorption rate and permeability of dsRNA-nanoparticle complexes and explored the RNAi controlling effect. Silencing the HpVAA gene was found to darken the epidermis of H. parallela larvae, with growth cessation or death or mortality, disrupting the epidermis and midgut structure. Quantitative reverse transcription-polymerase chain reaction and confocal microscopy confirmed the effective absorption of the dsRNA/LDH nanocomplex by peanut plants, with distribution in roots, stems, and leaves. Nanomaterial-mediated RNAi silenced the target genes, leading to the death of pests. Therefore, these findings indicate the successful application of the nanomaterial-mediated RNAi system for underground pests, thus establishing a theoretical foundation for developing a green, safe, and efficient pest control strategy.

Coexistence of liver abscess, hepatic cystic echinococcosis and hepatocellular carcinoma: A case report.

BACKGROUND: Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY: A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION: This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.

Stepwise Toward Pure Blue Organic Light-Emitting Diodes by Synergetically Locking and Shielding Carbonyl/Nitrogen-Based MR-TADF Emitters.

Deep-blue multi-resonance (MR) emitters with stable and narrow full-width-at-half-maximum (FWHM) are of great importance for widening the color gamut of organic light-emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen-based MR core. Intramolecularly locking carbonyl/nitrogen-based bears narrower emission of 2,10-dimethyl-12,12-diphenyl-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione in solution and further with peripheral-shielding groups, deep-blue emitter (12,12-diphenyl-2,10-bis(9-phenyl-9H-fluoren-9-yl)-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione, DPQAO-F) exhibits ultra-pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO-F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper-device of DPQAO-F exhibits a record-high EQEmax of 32.7% in the deep-blue region, representing the first example of carbonyl/nitrogen-based OLED that can concurrently achieve narrow bandwidth in the deep-blue region and a high electroluminescent efficiency surpassing 30%.

Malignant risk of pediatric Bethesda category III thyroid nodules subcategorized by nuclear atypia and other: A single institution experience.

BACKGROUND: The 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) divides AUS diagnoses into two major subcategories: atypia of undetermined significance (AUS) nuclear atypia (AUS-N) and other (AUS-O). This study aims to compare the histological outcome and malignant rate of pediatric AUS thyroid nodules classified into AUS-N and AUS-O subcategories. DESIGN: A search of our institutional electronic pathology database for the period from January 2012 to July 2023 was conducted to identify pediatric (<21 years old) thyroid nodules that were interpreted as AUS and subsequently had surgery. Cases were further divided into AUS-N and AUS-O subcategories. Results of follow-up surgical resections were collected. The malignant rate was calculated and compared between AUS-N and AUS-O groups. RESULTS: The study identified 62 thyroid nodules from 58 pediatric patients. Among these nodules, 29 and 33 were subcategorized as AUS-N and AUS-O, respectively. Both groups exhibited a female predominance and displayed a similar nodule size distribution. Histological analysis revealed 15 carcinomas in AUS-N nodules, including 11 cases of classic papillary thyroid carcinoma (PTC) and four cases of follicular type of PTC. In contrast, in the AUS-O group, a total of five carcinomas were documented, including two PTCs and three oncocytic thyroid carcinomas. Notably, the malignant rate of AUS-N nodules (52%) is significantly higher than that of AUS-O nodules (15%) (p = .002). CONCLUSION: In pediatric AUS thyroid nodules, the malignant risk in AUS-N is significantly higher than that in AUS-O. These findings may guide more appropriate clinical triage and/or improve management of pediatric patients with AUS thyroid nodules.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.

Transcriptional dynamics and regulatory function of milRNAs in Ascosphaera apis invading Apis mellifera larvae.

In the present study, small RNA (sRNA) data from Ascosphaera apis were filtered from sRNA-seq datasets from the gut tissues of A. apis-infected Apis mellifera ligustica worker larvae, which were combined with the previously gained sRNA-seq data from A. apis spores to screen differentially expressed milRNAs (DEmilRNAs), followed by trend analysis and investigation of the DEmilRNAs in relation to significant trends. Additionally, the interactions between the DEmilRNAs and their target mRNAs were verified using a dual-luciferase reporter assay. In total, 974 A. apis milRNAs were identified. The first base of these milRNAs was biased toward U. The expression of six milRNAs was confirmed by stem-loop RT-PCR, and the sequences of milR-3245-y and milR-10285-y were validated using Sanger sequencing. These miRNAs grouped into four significant trends, with the target mRNAs of DEmilRNAs involving 42 GO terms and 120 KEGG pathways, such as the fungal-type cell wall and biosynthesis of secondary metabolites. Further investigation demonstrated that 299 DEmilRNAs (novel-m0011-3p, milR-10048-y, bantam-y, etc.) potentially targeted nine genes encoding secondary metabolite-associated enzymes, while 258 (milR-25-y, milR-14-y, milR-932-x, etc.) and 419 (milR-4561-y, milR-10125-y, let-7-x, etc.) DEmilRNAs putatively targeted virulence factor-encoded genes and nine genes involved in the MAPK signaling pathway, respectively. Additionally, the interaction between ADM-B and milR-6882-x, as well as between PKIA and milR-7009-x were verified. Together, these results not only offer a basis for clarifying the mechanisms underlying DEmilRNA-regulated pathogenesis of A. apis and a novel insight into the interaction between A. apis and honey bee larvae, but also provide candidate DEmilRNA-gene axis for further investigation.

Ultrastable and supersensitive conductive hydrogels conferred by "sodium alginate stencil" anchoring strategy.

Although conductive hydrogels have been widely developed currently, their low sensitivity and poor stability severely limited their practical application in flexible wearable devices. Herein, a green "stencil" anchoring strategy was proposed in this study to engineer an ultra-stable and supersensitive hydrogel by virtue of polydopamine decorating sodium alginate molecular chains as "stencil" to anchor polyaniline as conductive component. The dispersion of polyaniline was significantly improved by the sodium alginate "stencil" in the conductive hydrogel. The developed conductive hydrogel exhibited outstanding properties that outperformed most conventional ones, including extraordinary sensitivity with a gauge factor of 38.2 and excellent stability with negligible shifting upon long-term cyclic stretching. Moreover, the conductive hydrogel displayed great self-adhesion and reliable self-healing performance endowed by its abundant catechol groups, hydrogen bondings and π-π stackings, respectively. Furthermore, the prepared hydrogel was also assembled as flexible strain and self-powered sensors, which displayed excellent sensing performance, indicating great potential in human-machine interactions, information transmission and road transportation.

Effects of environmental regulation on adjustment of agricultural industrial structure--An empirical study based on panel data of 31 provinces in China.

Using the panel data of 31 provinces in China between 2000 and 2018, this study theoretically and empirically analyses the impact of environmental regulations on the adjustment of the agriculture industrial structure from the perspectives of rationalisation and optimisation. Overall, variability in the impact of environmental regulation on the adjustment of the agricultural industrial structure is identified: a negative influence on the rationalisation of agricultural industrial structure and a positive influence on the optimisation of agricultural industrial structure. The impact of environmental regulations on the adjustment of agricultural industrial structure also reflects "large country characteristics": environmental regulations are more significant at the medium and low industrial structure levels. Environmental regulation significantly impacts the rationalisation of agricultural industrial structure in central and western regions and its optimisation in eastern and central regions. Through the panel threshold model test, this paper further finds that the effect of environmental regulations on the adjustment of agricultural industrial structure is not invariant. However, there is a non-linear relationship with significant threshold characteristics. Based on the above results, some countermeasures are suggested.

MXene Crosslinked Hydrogels with Low Hysteresis Conferred by Sliding Tangle Island Strategy.

Single-network hydrogels are often too fragile to withstand mechanical loading, whereas double-network hydrogels typically exhibit significant hysteresis during cyclic stretching-releasing process due to the presence of a sacrificial network. Consequently, it is a considerable challenge for designing hydrogels that are both low in hysteresis and high in toughness for applications requiring dynamic mechanical loads. Herein, the study introduced a novel "sliding tangle island" strategy for creating tough and low-hysteresis hydrogels, which are prepared through in situ polymerization of highly concentrated acrylamides (AM) to form numerous entanglements within the MXene spacing without any chemical crosslinker. The MXene entangled with long polyacrylamide (PAM) chains to form tangle island that served as a relay station to transmit stress to neighboring molecular chains. This mechanism helps alleviate stress concentration and enhances energy dissipation efficiency, thereby reducing mechanical hysteresis. The resulting hydrogel exhibited exceptional properties, including high stretchability (≈900%), low hysteresis (less than 7%), high toughness (1.34 MJ m-3), and excellent sensing performance to rival the commercial hydrogel electrode. Therefore, this work sheds light on feasible design of energy dissipation structure to reduce the hysteresis of the composite hydrogels.

Warming and altered precipitation independently and interactively suppress alpine soil microbial growth in a decadal-long experiment.

Warming and precipitation anomalies affect terrestrial carbon balance partly through altering microbial eco-physiological processes (e.g., growth and death) in soil. However, little is known about how such processes responds to simultaneous regime shifts in temperature and precipitation. We used the 18O-water quantitative stable isotope probing approach to estimate bacterial growth in alpine meadow soils of the Tibetan Plateau after a decade of warming and altered precipitation manipulation. Our results showed that the growth of major taxa was suppressed by the single and combined effects of temperature and precipitation, eliciting 40-90% of growth reduction of whole community. The antagonistic interactions of warming and altered precipitation on population growth were common (~70% taxa), represented by the weak antagonistic interactions of warming and drought, and the neutralizing effects of warming and wet. The members in Solirubrobacter and Pseudonocardia genera had high growth rates under changed climate regimes. These results are important to understand and predict the soil microbial dynamics in alpine meadow ecosystems suffering from multiple climate change factors.

Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia.

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.

Microalgal-bacterial treatment of ice-cream wastewater to remove organic waste and harvest oil-rich biomass.

The diversity of microalgae and bacteria allows them to form beneficial consortia for efficient wastewater treatment and nutrient recovery. This study aimed to evaluate the feasibility of a new microalgal-bacterial combination in the treatment of ice cream wastewater for biomass harvest. The bacterium Novosphingobium sp. ICW1 was natively isolated from ice cream wastewater and the microalga Vischeria sp. WL1 was a terrestrial oil-producing strain of Eustigmatophyceae. The ice cream wastewater was diluted 4 folds for co-cultivation, which was relatively less inhibitory for the growth of Vischeria sp. WL1. Four initial algal-bacterial combinations (v:v) of 150:0 (single algal cultivation), 150:1, 150:2, and 150:4 were assessed. During 24 days of co-cultivation, algal pigmentation was dynamically changed, particularly at the algal-bacterial combination of 150:4. Algal growth (in terms of cell number) was slightly promoted during the late phase of co-cultivation at the combinations of 150:2 and 150:4, while in the former the cellular oil yield was obviously elevated. Treated by these algal-bacterial combinations, total carbon was reduced by 67.5 ~ 74.5% and chemical oxygen demand was reduced by 55.0 ~ 60.4%. Although single bacterial treatment was still effective for removing organic nutrients, the removal efficiency was obviously enhanced at the algal-bacterial combination of 150:4. In addition, the harvested oils contained 87.1 ~ 88.3% monounsaturated fatty acids. In general, this study enriches the biotechnological solutions for the sustainable treatment of organic matter-rich food wastewater.

First Report of the Rust Fungus Melampsora ferrinii on Salix babylonica in China and a New Spermogonial and Aecial Host, Corydalis bungeana.

The occurrence of rust fungi on Corydalis bungeana Turcz. and Salix babylonica L. were found in same area of Hebei Province, China from 2022 to 2023. The life cycle connection of these rust fungi was suspected because Peng et al. (2022) reported the life cycle of Melampsora ferrinii Toome & Aime by inoculations, producing spermogonia and aecia on Corydalis species, and uredinia on S. babylonica. The morphology of the uredinial and telial stages on S. babylonica collected in the field was identical with the description of M. ferrinii by Toome and Aime (2015), and its identity was confirmed by phylogenetic analyses using the method of Ji et al. (2020) (LSU-PP087777, ITS-PP091274; Similarity with M. ferrinii: LSU-100%, ITS-99.85%). To confirm the life cycle of this rust fungus, inoculations were conducted on C. bungeana with basidiospores obtained from the teliospores on fallen leaves of Salix babylonica. The fallen leaves producing basidiospores were cut into small pieces (ca. 5 mm2) and placed on healthy leaves of C. bungeana. The inoculated plants were kept in a moist plastic box in darkness at 15-20℃ for 2 days and then transferred to the floor near windows at about 15-20℃ for observations. Ten days after inoculations small yellow spots of spermogonia appeared on the upper surface of the leaves of C. bungeana. About 7 days later, pale yellow aecia with aeciospores were produced mainly on the under surface of the leaves and petioles. The morphology of rust fungus on C. bungeana collected from the fields and obtained by inoculations was identical with the description by Peng et al. (2022). Phylogenetic analyses also showed that a specimen on C. bungeana collected from the field (LSU-OR607838, ITS-OR612063) were included into the same clade of M. ferrinii (Similarity: LSU-100 %, ITS-99.85). Based on morphology, inoculations and DNA sequence analyses, the rust fungi on C. bungeana and S. babylonica are identified as different stages of life cycle of M. ferrinii. This rust fungus has been reported to produce spermogonia and aecia on C. acuminata Franch., C. edulis Maxim. and C. racemosa (Thunb.) Pers. in China (Peng et al. 2022), and uredinia and telia on S. babylonica in USA, Argentina and Iran (Toome and Aime 2015, Abbasi et al. 2024), and on Salix sp. in Chile (Zapata 2016). Therefore, C. bungeana is a new host for M. ferrinii, and its field occurrence on S. babylonica is reported for the first time in China although Peng et al. (2022) reported successful results in its inoculations to S. babylonica in China. This report contributes to the control of rust diseases caused by this species. Specimens used in this experiment were deposited in the Fungal Herbarium of the Jilin Agricultural University, Changchun, China (HMJAU) and sequences newly analyzed were deposited in GenBank.

Immunogenicity and safety of boosting with a recombinant two-component SARS-CoV-2 vaccine: two randomized, parallel-controlled, phase 2 studies.

BACKGROUND: Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials. RESEARCH DESIGN AND METHODS: Study-1 involved subjects were randomized (1:1:1) to receive 20 µg ReCOV, 40 µg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 µg ReCOV (pilot batch, ReCOV HA), 20 µg ReCOV (commercial batch, ReCOV TC), or 30 µg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. RESULTS: Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence. CONCLUSIONS: Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV's potential for enhanced protection, supported by strong cross-neutralization and immune persistence. CLINICAL TRIAL REGISTRATION: Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids.

Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 µM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-ß-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study.

Dynamics and regulatory role of circRNAs in Asian honey bee larvae following fungal infection.

Non-coding RNA (ncRNA) plays a vital part in the regulation of immune responses, growth, and development in plants and animals. Here, the identification, characteristic analysis, and molecular verification of circRNAs in Apis cerana cerana worker larval guts were conducted, followed by in-depth investigation of the expression pattern of larval circRNAs during Ascosphaera apis infection and exploration of the potential regulatory part of differentially expressed circRNAs (DEcircRNAs) in host immune responses. A total of 3178 circRNAs in the larval guts of A. c. cerana were identified, with a length distribution ranging from 15 to 96,007 nt. Additionally, 155, 95, and 86 DEcircRNAs were identified in the in the 4-, 5-, and 6-day-old larval guts following A. apis infection. These DEcircRNAs were predicted to target 29, 25, and 18 parental genes relevant to 12, 20, and 17 GO terms as well as 144, 114, and 61 KEGG pathways, including 5 cellular and 4 humoral immune pathways. Complex competing endogenous RNA (ceRNA) regulatory networks were detected as being formed among DEcircRNAs, DEmiRNAs, and DEmRNAs. The target DEmRNAs were engaged in 36, 47, and 47 GO terms as well as 331, 332, and 331 pathways, including 6 cellular and 6 humoral immune pathways. Further, 19 DEcircRNAs, 5 DEmiRNAs, and 3 mRNAs were included in the sub-networks relative to 3 antioxidant enzymes. Finally, back-splicing sites within 15 circRNAs and the difference in the 15 DEcircRNAs' expression between uninoculated and A. apis-inoculated larval guts were confirmed based on molecular methods. These findings not only enrich our understanding of bee host-fungal pathogen interactions but also lay a foundation for illuminating the mechanism underlying the DEcircRNA-mediated immune defense of A. c. cerana larvae against A. apis invasion. KEY POINTS: • The expression pattern of circRNAs was altered in the A. cerana worker larval guts following A. apis infection. • Back-splicing sites within 15 A. cerana circRNAs were verified using molecular approaches. DEcircRNAs potentially modulated immune responses and antioxidant enzymes in A. apis-challenged host guts.