Strategy evolution on higher-order networks.

Cooperation is key to prosperity in human societies. Population structure is well understood as a catalyst for cooperation, where research has focused on pairwise interactions. But cooperative behaviors are not simply dyadic, and they often involve coordinated behavior in larger groups. Here we develop a framework to study the evolution of behavioral strategies in higher-order population structures, which include pairwise and multi-way interactions. We provide an analytical treatment of when cooperation will be favored by higher-order interactions, accounting for arbitrary spatial heterogeneity and nonlinear rewards for cooperation in larger groups. Our results indicate that higher-order interactions can act to promote the evolution of cooperation across a broad range of networks, in public goods games. Higher-order interactions consistently provide an advantage for cooperation when interaction hyper-networks feature multiple conjoined communities. Our analysis provides a systematic account of how higher-order interactions modulate the evolution of prosocial traits.

Characterization and elimination efficiency of volatile organic compounds in mechanically recycled polyethylene terephthalate at various recycling stages.

The recycling of polyethylene terephthalate (PET) stands as an effective strategy for mitigating plastic pollution and reducing resource waste. The study aimed to investigate the characterization and elimination efficiency of volatile organic compounds (VOCs) present in rPET at various recycling stages using comprehensive two-dimensional gas chromatography-quadrupole-time-of-flight-mass spectrometry coupled with chemometrics. The results revealed that 52, 135, 95, 44, and 33 VOCs, mostly classified into three chemical groups, were tentatively identified in virgin - PET (v-PET), cold water washed - rPET (C-rPET), decontaminated - rPET (D-rPET), melt-extruded - rPET (M-rPET), and solid-state polycondensation - rPET (S-rPET), respectively. Regarding the VOCs with high and median detection frequencies, fatty acyls showed the highest elimination efficiency (100 % and 92 %), followed by organooxygen compounds (81 % and 99 %), others (97 % and 95 %), and benzene and substituted derivatives (82 % and 95 %) in term of HS-SPME. Following the recycling process, there was a general decrease in the concentration of almost all VOCs, as evidenced by the substantial reduction of o-Xylene, hexanoic acid, octanal, and D-limonene from 18.11, 22.43, 30.74, and 7.41 mg/kg to 0, 0, 3.97, and 0 mg/kg, respectively. However, it was noteworthy that the VOCs identified in the samples were not completely extracted, owing to the limitations of HS-SPME. Furthermore, chemometrics analysis indicated significant discrimination among VOCs from vPET, C-rPET, D-rPET, and M-rPET, while indistinct differences were observed between M-rPET and S-rPET. This study contributes to the enhancement of the recycling process and emphasizes the importance of safeguarding consumer health in terms of elimination of VOCs.

The gut microbiome associates with phenotypic manifestations of post-acute COVID-19 syndrome.

The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrates that the gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS.

Sensitive Fluorescent Biosensor Reveals Differential Subcellular Regulation of PKC.

The protein kinase C (PKC) family of serine/threonine kinases, which consist of three distinctly regulated subfamilies, have long been established as critical for a variety of cellular functions. However, how PKC enzymes are regulated at different subcellular locations, particularly at emerging signaling hubs such as the ER, lysosome, and Par signaling complexes, is unclear. Here, we present a sensitive Excitation Ratiometric (ExRai) C Kinase Activity Reporter (ExRai-CKAR2) that enables the detection of minute changes in subcellular PKC activity. Using ExRai-CKAR2 in conjunction with an enhanced diacylglycerol (DAG) biosensor capable of detecting intracellular DAG dynamics, we uncover the differential regulation of PKC isoforms at distinct subcellular locations. We find that G-protein coupled receptor (GPCR) stimulation triggers sustained PKC activity at the ER and lysosomes, primarily mediated by Ca2+ sensitive conventional PKC (cPKC) and novel PKC (nPKC), respectively, with nPKC showing high basal activity due to elevated basal DAG levels on lysosome membranes. The high sensitivity of ExRai-CKAR2, targeted to either the cytosol or Par-complexes, further enabled us to detect previously inaccessible endogenous atypical PKC (aPKC) activity in 3D organoids. Taken together, ExRai-CKAR2 is a powerful tool for interrogating PKC regulation in response to physiological stimuli.

Corydalis sunhangii (Papaveraceae): A new species from Xizang, China, based on plastome and morphological data.

A new species of Papaveraceae, Corydalis sunhangii, in the section Trachycarpae, is described and illustrated from Nyingchi City, Xizang, China. The new species has some resemblance to Corydalis kingdonis, but differs by radical leaves prominent, usually several, blade tripinnate (vs. insignificant, few, blade bi- to triternate); cauline leaf usually one, much smaller than radical leaves, usually situated in lower half of stem (vs. usually two, larger than radical leaves, concentrated in upper third of stem); racemes densely 13-35-flowered (vs. rather lax, 4-11-flowered); claw of lower petal shallowly saccate (vs. very prominently and deeply saccate); capsule oblong, with raised lines of dense papillae (vs. broadly obovoid, smooth). Phylogenetic analysis, based on 68 protein-coding plastid genes of 49 samples, shows that C. sunhangii is not closely related to any hitherto described species, which is consistent with our morphological analysis.

Diallyl disulfide antagonizes DJ-1 mediated proliferation, epithelial-mesenchymal transition, and chemoresistance in gastric cancer cells.

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

GhCOL2 Positively Regulates Flowering by Activating the Transcription of GhHD3A in Upland Cotton (Gossypium hirsutum L.).

Plants have evolved sophisticated signaling networks to adjust flowering time, ensuring successful reproduction. Two crucial flowering regulators, FLOWERING LOCUS T (FT) and CONSTANS (CO), play pivotal roles in regulating flowering across various species. Previous studies have indicated that suppressing Gossypium hirsutum CONSTANS-LIKE 2 (GhCOL2), a homolog of Arabidopsis CO, leads to delayed flowering in cultivated cotton. However, the underlying regulatory mechanisms remain unknown. In this study, a yeast one-hybrid and dual-LUC expression assays were used to elucidate the molecular mechanism through which GhCOL2 regulates the transcription of GhHD3A. RT-qPCR was used to examine the expression of GhCOL2 and GhHD3A. Our findings reveal that GhCOL2 directly binds to CCACA cis-elements and atypical CORE (TGTGTATG) cis-elements in the promoter regions of HEADING DATE 3 A (HD3A), thereby activating GhHD3A transcription. Notably, GhCOL2 and GhHD3A exhibited high expression levels in the adult stage and low levels in the juvenile stage. Interestingly, the expression of GhCOL2 and GhHD3A varied significant between the two cotton varieties (Tx2094 and Maxxa). In summary, our study enhances the understanding of the molecular mechanism by which cotton GhCOL2-GhHD3A regulates flowering at the molecular level. Furthermore, it contributes to a broader comprehension of the GhCOL2-GhHD3A model in G. hirsutum.

Parkin deficiency promotes liver cancer metastasis by TMEFF1 transcription activation via TGF-ß/Smad2/3 pathway.

Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-ß production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-ß inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1ß and p53, which accounts for the suppression of TGF-ß production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-ß/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.

Site-specific albumin tagging with NIR-II fluorogenic dye for high-performance and super-stable bioimaging.

Synthetic near-infrared-II (NIR-II) dyes are promising for deep tissue imaging, yet they are generally difficult to target a given biomolecule with high specificity. Furthermore, the interaction mechanism between albumin and cyanine molecules, which is usually regarded as uncertain "complexes" such as crosslinked nanoparticles, remains poorly understood. Methods: Here, we propose a new class of NIR-II fluorogenic dyes capable of site-specific albumin tagging for in situ albumin seeking/targeting or constructing high-performance cyanine@albumin probes. We further investigate the interaction mechanism between NIR-II fluorogenic dyes and albumin. Results: We identify CO-1080 as an optimal dye structure that produces a stable/bright NIR-II cyanine@albumin probe. CO-1080 exhibits maximum supramolecular binding affinity to albumin while catalyzing their covalent attachment. The probe shows exact binding sites located on Cys476 and Cys101, as identified by proteomic analysis and docking modeling. Conclusion: Our cyanine@albumin probe substantially improves the pharmacokinetics of its free dye counterpart, enabling high-performance NIR-II angiography and lymphography. Importantly, the site-specific labeling tags between NIR-II fluorogenic dyes and albumin occur under mild conditions, offering a specific and straightforward synthesis strategy for NIR-II fluorophores in the fields of targeting bioimaging and imaging-guided surgery.

Potential safety concerns of volatile constituents released from coffee-ground-blended single-use biodegradable drinking straws: A chemical space perspective.

Incorporating spent coffee grounds into single-use drinking straws for enhanced biodegradability also raises safety concerns due to increased chemical complexity. Here, volatile organic compounds (VOCs) present in coffee ground straws (CGS), polylactic acid straws (PLAS), and polypropylene straws (PPS) were characterized using headspace - solid-phase microextraction and migration assays, by which 430 and 153 VOCs of 10 chemical categories were identified by gas chromatography - mass spectrometry, respectively. Further, the VOCs were assessed for potential genetic toxicity by quantitative structure-activity relationship profiling and estimated daily intake (EDI) calculation, revealing that the VOCs identified in the CGS generally triggered the most structural alerts of genetic toxicity, and the EDIs of 37.9% of which exceeded the threshold of 0.15 µg person-1 d-1, also outnumbering that of the PLAS and PPS. Finally, 14 VOCs were prioritized due to their definite hazards, and generally higher EDIs or detection frequencies in the CGS. Meanwhile, the probability of producing safer CGS was also illustrated. Moreover, it was uncovered by chemical space that the VOCs with higher risk potentials tended to gather in the region defined by the molecular descriptor related to electronegativity or octanol/water partition coefficient. Our results provided valuable references to improve the chemical safety of the CGS, to promote consumer health, and to advance the sustainable development of food contact materials.

Long-distance transmission of arbitrary quantum states between spatially separated microwave cavities.

Long-distance transmission between spatially separated microwave cavities is a crucial area of quantum information science and technology. In this work, we present a method for achieving long-distance transmission of arbitrary quantum states between two microwave cavities, by using a hybrid system that comprises two microwave cavities, two nitrogen-vacancy center ensembles (NV ensembles), two optical cavities, and an optical fiber. Each NV ensemble serves as a quantum transducer, dispersively coupling with a microwave cavity and an optical cavity, which enables the conversion of quantum states between a microwave cavity and an optical cavity. The optical fiber acts as a connector between the two optical cavities. Numerical simulations demonstrate that our method allows for the transfer of an arbitrary photonic qubit state between two spatially separated microwave cavities with high fidelity. Furthermore, the method exhibits robustness against environmental decay, parameter fluctuations, and additive white Gaussian noise. Our approach offers a promising way for achieving long-distance transmission of quantum states between two spatially separated microwave cavities, which may have practical applications in networked large-scale quantum information processing and quantum communication.

Occurrence and prioritization of non-volatile substances in recycled PET flakes produced in China.

Recycled PET (rPET) is gaining popularity for use in the production of new food contact materials (FCMs) under the context of circular economy. However, the limited information on contaminants in rPET from China and concerns about their potential risk are major obstacles to their use in FCM in China. Fifty-five non-volatile compounds were tentatively identified in 126 batches of hot-washed rPET flakes aimed for food packaging applications in China. Although the 55 substances are not necessarily migratable and may not end up in the contacting media, their presence indicates a need for proper management and control across the value chain. For this reason, the 55 substances prioritized on the basis of level of concerns and in-silico genotoxicity profiler. Among them, dimethoxyethyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate were classified as level V substances, and Michler's ketone and 4-nitrophenol were both categorized as level V substances and had the genotoxic structure alert, while 2,4,5-trimethylaniline was specified with genotoxic structure alert. The above substances have high priority and may pose a potential risk to human health, therefore special attention should be paid to their migration from rPET. Aside from providing valuable information on non-volatile contaminants present in hot-washed rPET flakes coming from China, this article proposed a prioritization workflow that can be of great help to identify priority substances deserving special attention across the value chain.

Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein-protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management.

dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing.

Due to its highly insidious and rapid progression, deep tissue pressure injury (DTPI) is a clinical challenge. Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accumulation. Decellularized extracellular matrix (dECM) hydrogel promotes skeletal muscle injury repair. However, its role in polarizing macrophages and regulating iron metabolism in DTPI remains unclear. Here, porcine dECM hydrogel was prepared, and its therapeutic function and mechanism in repairing DTPI were investigated. The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD206+ macrophages and notably decreased intracellular divalent iron levels. In mice DTPI model, dECM hydrogel treatment promoted M1 to M2 macrophage conversion, improved iron metabolism and reduced oxidative stress in the early stage of DTPI. In the remodeling phase, the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair. Furthermore, the immunomodulation of dECM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway, as revealed by GO and KEGG pathway analysis, which may ameliorate the iron deposition and promote the healing of DTPI. Our findings indicate that dECM hydrogel is promising in skeletal muscle repair, inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

A promising natural product in diffuse large B-cell lymphoma therapy by targeting PIM1.

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive type of B-cell lymphoma. Unfortunately, about one-third of patients either relapse after the initial treatment or are refractory to first-line therapy, indicating a need for new treatment modalities. PIM serine/threonine kinases are proteins that are associated with genetic mutations, overexpression, or translocation events in B-cell lymphomas. We conducted an integrative analysis of whole-exome sequencing in 52 DLBCL patients, and no amplification, mutation, or translocation of the PIM1 gene was detected. Instead, analyses of TCGA and GTEx databases identified that PIM1 expression was increased in DLBCL samples compared to normal tissue, and high expression levels were associated with poor overall survival. Moreover, interference of PIM1 significantly suppressed DLBCL cell proliferation. In addition, we identified anwulignan, a natural small-molecule compound, as a PIM1 inhibitor. Anwulignan directly binds to PIM1 and exerts antitumor effects on DLBCL in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagic cell death. Furthermore, we identified an effective synergistic combination between anwulignan and chidamide. Our findings suggested that PIM1 could be a therapeutic target and prognostic factor for DLBCL, and anwulignan holds promise for future development as a natural product for treatment.

Alterations in fecal virome and bacteriome virome interplay in children with autism spectrum disorder.

Emerging evidence suggests autism spectrum disorder (ASD) is associated with altered gut bacteria. However, less is known about the gut viral community and its role in shaping microbiota in neurodevelopmental disorders. Herein, we perform a metagenomic analysis of gut-DNA viruses in 60 children with ASD and 64 age- and gender-matched typically developing children to investigate the effect of the gut virome on host bacteria in children with ASD. ASD is associated with altered gut virome composition accompanied by the enrichment of Clostridium phage, Bacillus phage, and Enterobacteria phage. These ASD-enriched phages are largely associated with disrupted viral ecology in ASD. Importantly, changes in the interplay between the gut bacteriome and virome seen in ASD may influence the encoding capacity of microbial pathways for neuroactive metabolite biosynthesis. These findings suggest an impaired bacteriome-virome ecology in ASD, which sheds light on the importance of bacteriophages in pathogenesis and the development of microbial therapeutics in ASD.

One-Shot Weakly-Supervised Segmentation in 3D Medical Images.

Deep neural networks typically require accurate and a large number of annotations to achieve outstanding performance in medical image segmentation. One-shot and weakly-supervised learning are promising research directions that reduce labeling effort by learning a new class from only one annotated image and using coarse labels instead, respectively. In this work, we present an innovative framework for 3D medical image segmentation with one-shot and weakly-supervised settings. Firstly a propagation-reconstruction network is proposed to propagate scribbles from one annotated volume to unlabeled 3D images based on the assumption that anatomical patterns in different human bodies are similar. Then a multi-level similarity denoising module is designed to refine the scribbles based on embeddings from anatomical- to pixel-level. After expanding the scribbles to pseudo masks, we observe the miss-classified voxels mainly occur at the border region and propose to extract self-support prototypes for the specific refinement. Based on these weakly-supervised segmentation results, we further train a segmentation model for the new class with the noisy label training strategy. Experiments on three CT and one MRI datasets show the proposed method obtains significant improvement over the state-of-the-art methods and performs robustly even under severe class imbalance and low contrast. Code is publicly available at https://github.com/LWHYC/OneShot_WeaklySeg.

CYP4CS5-mediated thiamethoxam and clothianidin resistance is accompanied by fitness cost in the whitefly Bemisia tabaci.

BACKGROUND: Understanding the trade-offs between insecticide resistance and the associated fitness is of particular importance to sustainable pest control. One of the most devastating pest worldwide, the whitefly Bemisia tabaci, has developed resistance to various insecticides, especially the neonicotinoid group. Although neonicotinoid resistance often is conferred by P450s-mediated metabolic resistance, the relationship between such resistance and the associated fitness phenotype remains largely elusive. By gene cloning, quantitative reverse transcription (qRT)-PCR, RNA interference (RNAi), transgenic Drosophila melanogaster, metabolism capacity in vitro and 'two sex-age stage' life table study, this study aims to explore the molecular role of a P450 gene CYP4CS5 in neonicotinoid resistance and to investigate whether such resistance mechanism carries fitness costs in the whitefly. RESULTS: Our bioassay tests showed that a total of 13 field-collected populations of B. tabaci MED biotype displayed low-to-moderate resistance to thiamethoxam and clothianidin. Compared to the laboratory susceptible strain, we then found that an important P450 CYP4CS5 was remarkably upregulated in the field resistant populations. Such overexpression of CYP4CS5 had a good match with the resistance level among the whitefly samples. Further exposure to the two neonicotinoids resulted in an increase in CYP4CS5 expression. These results implicate that overexpression of CYP4CS5 is closely correlated with thiamethoxam and clothianidin resistance. RNAi knockdown of CYP4CS5 increased mortality of the resistant and susceptible populations after treatment with thiamethoxam and clothianidin in bioassay, but obtained an opposite result when using a transgenic line of D. melanogaster expressing CYP4CS5. Metabolic assays in vitro revealed that CYP4CS5 exhibited certain capacity of metabolizing thiamethoxam and clothianidin. These in vivo and in vitro assays indicate an essential role of CYP4CS5 in conferring thiamethoxam and clothianidin resistance in whitefly. Additionally, our life-table analysis demonstrate that the field resistant whitefly exhibited a prolonged development time, shortened longevity and reduced fecundity compared to the susceptible, suggesting an existing fitness cost as a result of the resistance. CONCLUSION: Collectively, in addition to the important role of CYP4CS5 in conferring thiamethoxam and clothianidin resistance, this resistance mechanism is associated with fitness costs in the whitefly. These findings not only contribute to the development of neonicotinoids resistance management strategies, but also provide a new target for sustainable whitefly control. © 2023 Society of Chemical Industry.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.