Hepatitis E virus infection remodels the mature tRNAome in macrophages to orchestrate NLRP3 inflammasome response.

Hepatitis E virus (HEV) infection has been shown to activate NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in macrophages, a key mechanism of causing pathological inflammation, but the mechanisms regulating this response remain poorly understood. Here, we report that the mature tRNAome dynamically responds to HEV infection in macrophages. This directs IL-1ß expression, the hallmark of NLRP3 inflammasome activation, at mRNA and protein levels. Conversely, pharmacological inhibition of inflammasome activation abrogates HEV-provoked tRNAome remodeling, revealing a reciprocal interaction between the mature tRNAome and the NLRP3 inflammasome response. Remodeling the tRNAome results in improved decoding of codons directing leucine- and proline synthesis, which are the major amino acid constituents of IL-1ß protein, whereas genetic or functional interference with tRNAome-mediated leucine decoding impairs inflammasome activation. Finally, we demonstrated that the mature tRNAome also actively responds to lipopolysaccharide (a key component of gram-negative bacteria)-triggered inflammasome activation, but the response dynamics and mode of actions are distinct from that induced by HEV infection. Our findings thus reveal the mature tRNAome as a previously unrecognized but essential mediator of host response to pathogens and represent a unique target for developing anti-inflammatory therapeutics.

Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation.

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in a translation initiation complex reveals unknown interactions between the ACT domain of Rsh and components of the ribosomal L7/L12 stalk base, suggesting that the aminoacylation status of A-site tRNA is surveilled during the first cycle of elongation. Altogether, we propose a surveillance model of Rsh activation that originates from its constitutive interaction with the ribosomes entering the translation cycle.

A Novel Induction-Type Pressure Sensor based on Magneto-Stress Impedance and Magnetoelastic Coupling Effect for Monitoring Hand Rehabilitation.

Visualization of training effectiveness is critical to patients' confidence and eventual rehabilitation. Here, an innovative magnetoinductive pressure sensor is proposed for monitoring hand rehabilitation in stroke hemiplegic patients. It couples the giant magneto and stress-impedance effects of a square spiral amorphous wire with the giant magnetoelastic effect of a polymer magnet (NdFeB@PDMS). The addition of the magnetoelastic layer results in a sensitivity improvement of 178%, a wide sensing range (up to 1 MPa), fast response/recovery times (40 ms), and excellent mechanical robustness (over 15 000 cycles). Further integration with an LC oscillation circuit enables frequency adjustment into the MHz range resulting in a sensitivity of 6.6% kPa-1 and outstanding linearity (R2 =  0.99717) over a stress range of up to 100 kPa. When attached to a commercial split-fingerboard, the sensor is capable of dynamically monitoring the force in each finger, providing a reading of the rehabilitation process. Unlike conventional inductive sensors, the sensor is based on an inductive force-responsive material (amorphous wire), which significantly boosts the sensitivity. The approach also demonstrates the potential of magnetoelasticity in static pressure sensing, which is highly sensitive to dynamic pressure only through electromagnetic induction. This makes it more suitable for long-term and continuous human health monitoring.

ß-hydroxybutyrate inhibits malignant phenotypes of prostate cancer cells through ß-hydroxybutyrylation of indoleacetamide-N-methyltransferase.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent cancers in men and is associated with high mortality and disability rates. ß-hydroxybutyrate (BHB), a ketone body, has received increasing attention for its role in cancer. However, its role in PCa remains unclear. This study aimed to explore the mechanism and feasibility of BHB as a treatment alternative for PCa. METHODS: Colony formation assay, flow cytometry, western blot assay, and transwell assays were performed to determine the effect of BHB on the proliferation and metastasis of PCa cells. Tumor sphere formation and aldehyde dehydrogenase assays were used to identify the impact of BHB or indoleacetamide-N-methyltransferase (INMT) on the stemness of PCa cells. N6-methyladenosine (m6A)-meRIP real-time reverse transcription polymerase chain reaction and dual luciferase assays were conducted to confirm INMT upregulation via the METTL3-m6A pathway. Co-IP assay was used to detect the epigenetic modification of INMT by BHB-mediated ß-hydroxybutyrylation (kbhb) and screen enzymes that regulate INMT kbhb. Mouse xenograft experiments demonstrated the antitumor effects of BHB in vivo. RESULTS: BHB can inhibit the proliferation, migration, and invasion of PCa cells by suppressing their stemness. Mechanistically, INMT, whose expression is upregulated by the METTL3-m6A pathway, was demonstrated to be an oncogenic gene that promotes the stem-like characteristics of PCa cells. BHB can suppress the malignant phenotypes of PCa by kbhb of INMT, which in turn inhibits INMT expression. CONCLUSIONS: Our findings indicate a role of BHB in PCa metabolic therapy, thereby suggesting an epigenetic therapeutic strategy to target INMT in aggressive PCa. TRIAL REGISTRATION: Not applicable.

Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors worldwide with a dismal prognosis and high relapse rate. PDAC is considered a "cold cancer" for which immunotherapy is not effective. Therefore, to improve the prognosis for PDAC patients, it is urgent to explore the mechanism driving its insensitivity to immunotherapy. MATERIALS AND METHODS: We conducted pancancer analyses to test IGF2BP family expression and survival in patients with different cancers via TCGA and GETx databases. Then, we determined the immunological role and prognostic value of IGF2BP2 in vitro, in vivo and in clinical specimens. RESULTS: In the present study, we found that the m6A reader IGF2BP2 was the most clinically relevant member of the IGF2BP family for pancreatic cancer. High expression of IGF2BP2 was most associated with poor prognosis and an immunosuppressive microenvironment in PDAC. By IGF2BP2 knockdown, we found that tumor cell proliferation and invasive ability were significantly diminished. Importantly, we found that IGF2BP2 expression was closely associated with high expression of immunosuppressive molecules such as PD-L1. IGF2BP2 modulated downstream PD-L1 expression by regulating its mRNA stability via m6A methylation control, and we obtained the same verification in animal experiments and human tissue specimens. CONCLUSION: Our study contributes to existing knowledge regarding the IGF2BP2-regulated PD-L1 signaling pathway as a potential prognostic and immune biomarker in pancreatic cancer.

Structure-based design and synthesis of anti-fibrotic compounds derived from para-positioned 3,4,5-trisubstituted benzene.

Liver fibrosis is an abnormal wound-healing response to liver injuries. It can lead to liver cirrhosis, and even liver cancer and liver failure. There is a lack of treatment for liver fibrosis and it is of great importance to develop anti-fibrotic drugs. A pivotal event in the process of developing liver fibrosis is the activation of hepatic stellate cells (HSCs), in which the nuclear receptor Nur77 plays a crucial role. This study aimed to develop novel anti-fibrotic agents with Nur77 as the drug target by modifying the structure of THPN, a Nur77-binding and anti-melanoma compound. Specifically, a series of para-positioned 3,4,5-trisubstituted benzene ring compounds with long-chain backbone were generated and tested for anti-fibrotic activity. Among these compounds, compound A8 was with the most potent and Nur77-dependent inhibitory activity against TGF-ß1-induced activation of HSCs. In a crystal structure analysis, compound A8 bound Nur77 in a peg-in-hole mode as THPN did but adopted a different conformation that could interfere the Nur77 interaction with AKT, which was previous shown to be important for an anti-fibrotic activity. In a cell-based assay, compound A8 indeed impeded the interaction between Nur77 and AKT leading to the stabilization of Nur77 without the activation of AKT. In a mouse model, compound A8 effectively suppressed the activation of AKT signaling pathway and up-regulated the cellular level of Nur77 to attenuate the HSCs activation and ameliorate liver fibrosis with no significant toxic side effects. Collectively, this work demonstrated that Nur77-targeting compound A8 is a promising anti-fibrotic drug candidate.

Design of a dual hollow beam optical antenna based on a Fresnel lens-conical lens combination.

To improve the transmission efficiency of Cassegrain antennas and enable the simultaneous transmission of signals with different wavelengths in the antenna system, this study introduces Fresnel lenses and conical lenses in front of the Cassegrain antenna at the transmitting end. Reflective mirrors and focusing lenses are introduced at the receiving end. A detailed description is provided of the design process for the Fresnel lens, as well as the impact of various parameters on the hollow radius when combined with the conical lens. Based on the laws of vector reflection and refraction, simulations are performed to track the propagation of light through the entire communication system and lens pairs, providing transmission efficiency plots of the antenna system under deflection and off-axis conditions. Taking into account practical factors such as lens chamfer, transmittance, Cassegrain antenna reflectance, and material dispersion, the transmission efficiency of the antenna system at 1550 nm wavelength can still reach 93.45%. The proposed method not only improves the transmission efficiency of Cassegrain antennas, but also enables the transmission of different information through the inner and outer layers of the antenna system.

Radiometric thermometry of point targets based on dual-band infrared imaging.

The observation area of a point target, which is usually inaccessible, is a necessary condition when utilizing the conventional single-band infrared radiometric thermometry method, as the image gray level inevitably undergoes dispersion. Otherwise, significant errors will be generated, seriously affecting the applicability of infrared radiometric thermometry for distant point targets in the external field. To address the above issue, the infrared radiometric thermometry method for point targets has been researched. A point target radiometric thermometry method based on dual-band infrared imaging is proposed, which can effectively measure radiance and temperature when the area of the point target is unknown. The experimental results show that, compared with conventional single-band algorithms, the proposed dual-band point target thermometry algorithm has a maximum error of 11.18°C under the condition of unknown area, which can meet the needs of infrared radiometric thermometry of point targets at long distances in the external field.

Hepatitis E virus infection upregulates ING5 expression in vitro and in vivo.

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. Immunocompromised individuals infected by HEV are prone to chronic hepatitis and increase the risk of hepato-cellular carcinoma (HCC). Inhibitor of growth family member 5 (ING5) is a tumor suppressor that is expressed at low levels in cancer tumors or cells. However, the underlying relationship between ING5 and HEV infection is unclear. In the present study, acute and chronic HEV animal models are used to explore the interaction between ING5 and HEV. Notably, the expression of ING5 is significantly increased in both the livers of acute HEV-infected BALB/c mice and chronic HEV-infected rhesus macaques. In addition, the relationship between HEV infection and ING5 expression is further identified in human hepatoma (HepG-2) cells. In conclusion, HEV infection strongly upregulates ING5 expression both in vivo and in vitro, which has significant implications for further understanding the pathogenic mechanism of HEV infection.

An Improved Method for Detecting Crane Wheel-Rail Faults Based on YOLOv8 and the Swin Transformer.

In the realm of special equipment, significant advancements have been achieved in fault detection. Nonetheless, faults originating in the equipment manifest with diverse morphological characteristics and varying scales. Certain faults necessitate the extrapolation from global information owing to their occurrence in localized areas. Simultaneously, the intricacies of the inspection area's background easily interfere with the intelligent detection processes. Hence, a refined YOLOv8 algorithm leveraging the Swin Transformer is proposed, tailored for detecting faults in special equipment. The Swin Transformer serves as the foundational network of the YOLOv8 framework, amplifying its capability to concentrate on comprehensive features during the feature extraction, crucial for fault analysis. A multi-head self-attention mechanism regulated by a sliding window is utilized to expand the observation window's scope. Moreover, an asymptotic feature pyramid network is introduced to augment spatial feature extraction for smaller targets. Within this network architecture, adjacent low-level features are merged, while high-level features are gradually integrated into the fusion process. This prevents loss or degradation of feature information during transmission and interaction, enabling accurate localization of smaller targets. Drawing from wheel-rail faults of lifting equipment as an illustration, the proposed method is employed to diagnose an expanded fault dataset generated through transfer learning. Experimental findings substantiate that the proposed method in adeptly addressing numerous challenges encountered in the intelligent fault detection of special equipment. Moreover, it outperforms mainstream target detection models, achieving real-time detection capabilities.

Polysaccharide from Artocarpus heterophyllus Lam. (Jackfruit) Pulp Ameliorates Dextran Sodium Sulfate-Induced Enteritis in Rats.

A polysaccharide from Artocarpus heterophyllus Lam. (jackfruit) pulp (JFP-Ps) is known for its excellent bioactivities. However, its impact on small intestinal barrier function is still largely unexplored. The study aimed to examine the protection effect of JFP-Ps against dextran sodium sulfate-induced enteritis and its underlying mechanism. This research revealed that JFP-Ps mitigated small intestinal tissue damage by reducing the expression of pro-inflammatory cytokines and promoting the expression of the anti-inflammatory cytokine interleukin-10 in the small intestine. JFP-Ps diminished oxidative stress by bolstering the activity of antioxidant enzymes and reducing the concentration of malondialdehyde in the small intestine. In addition, JFP-Ps may restore the mechanical barrier and inhibit intestinal structure damage by augmenting the expression of short-chain fatty acids (SCFAs) receptors (GPR41/43) and up-regulating the expression of tight junction proteins (occludin). In conclusion, JFP-Ps may positively influence intestinal health by relieving oxidative stress in the small intestine, improving mechanical barrier function, activating the SCFA-GPR41/GPR43 axis, and inhibiting TLR4/MAPK pathway activation. The results augment our comprehension of the bioactivities of JFP-Ps, corroborating its great potential as a functional food.

Factors influencing traumatic brain injuries in maxillofacial fractures: A 12-year retrospective analysis of 2841 patients.

BACKGROUND/AIM: Results of studies investigating the association between traumatic brain injury (TBI) and maxillofacial fractures (MFs) have varied considerably. The present study aimed to evaluate the correlation between TBIs and MFs, as well as the impact of age, sex, trauma mechanism, and season on TBIs. MATERIALS AND METHODS: This 12-year retrospective study of 2841 patients used univariate and multivariate logistic regression to assess the association between MFs and other factors impacting TBIs. RESULTS: Among 2841 patients, 1978 TBIs occurred in 829 (29.2%), with intracranial injuries (n = 828) is the most common. Of 829 patients with TBIs, 688 were male and 141 were female, corresponding to a male-to-female ratio of 4.9:1.0. The most common age group was 40-49 years (24.6%). Vehicles (including motor vehicles and electric vehicles) accidents were the primary causes of injuries. Multivariate regression analyses revealed an increased risk for TBIs among males (odds ratio [OR] 0.632, p < 0.001). Patients >40 years of age were at higher risk for TBIs, especially those ≥70 years (OR 3.966, p = 0.001). Vehicle accidents were a high-risk factor for TBIs (OR 6.894, p < 0.001), and winter was the most prevalent season for such injuries (OR 1.559, p = 0.002). Risk for TBI increased by 136.4% in combined midfacial and mandibular fractures (p = 0.016) and by 101.6% in multiple midfacial fractures (p = 0.045). TBIs were less common in single mandibular fractures, notably in single-angle fractures, with a risk of only 0.204-fold. CONCLUSION: TBIs in MFs were significantly correlated with sex, age, aetiology, season and fracture location. Maxillofacial surgeons and emergency physicians must be aware of the possible association between TBIs and MFs to assess and manage this complicated relationship in a timely manner.

Identification of Multiple Genetic Loci Related to Low-Temperature Tolerance during Germination in Maize (Zea maize L.) through a Genome-Wide Association Study.

Low-temperature stress during the germination stage is an important abiotic stress that affects the growth and development of northern spring maize and seriously restricts maize yield and quality. Although some quantitative trait locis (QTLs) related to low-temperature tolerance in maize have been detected, only a few can be commonly detected, and the QTL intervals are large, indicating that low-temperature tolerance is a complex trait that requires more in-depth research. In this study, 296 excellent inbred lines from domestic and foreign origins (America and Europe) were used as the study materials, and a low-coverage resequencing method was employed for genome sequencing. Five phenotypic traits related to low-temperature tolerance were used to assess the genetic diversity of maize through a genome-wide association study (GWAS). A total of 14 SNPs significantly associated with low-temperature tolerance were detected (-log10(P) > 4), and an SNP consistently linked to low-temperature tolerance in the field and indoors during germination was utilized as a marker. This SNP, 14,070, was located on chromosome 5 at position 2,205,723, which explained 4.84-9.68% of the phenotypic variation. The aim of this study was to enrich the genetic theory of low-temperature tolerance in maize and provide support for the innovation of low-temperature tolerance resources and the breeding of new varieties.

Synergistic Ionic Liquid in Hole Transport Layers for Highly Stable and Efficient Perovskite Solar Cells.

Perovskite solar cells (PSCs) with n-i-p structures often utilize an organic 2,2',7,7'-tetrakis (N, N-di-p-methoxyphenyl-amine) 9,9'-spirobifluorene (spiro-OMeTAD) along with additives of lithium bis(trifluoromethanesulfonyl)imide salt (LiTFSI) and tert-butylpyridine as the hole transporting layer (HTL). However, the HTL lacks stability in ambient air, and numerous defects are often present on the perovskite surface, which is not conducive to a stable and efficient PSC. Therefore, constructive strategies that simultaneously stabilize spiro-OMeTAD and passivate the perovskite surface are required. In this work, it is demonstrated that a novel ionic liquid of dimethylammonium bis(trifluoromethanesulfonyl)imide (DMATFSI) could act as a bifunctional HTL modulator in n-i-p PSCs. The addition of DMATFSI into spiro-OMeTAD can effectively stabilize the oxidized spiro-OMeTAD+ cation radicals through the formation of spiro-OMeTAD+ TFSI- because of the excellent charge delocalization of the conjugated CF3 SO2 - moiety within TFSI- . In addition, DMA+ cations could move toward the perovskite from the HTL, resulting in the passivation of defects at the perovskite surface. Accordingly, a power conversion efficiency of 23.22% is achieved for PSCs with DMATFSI and LiTFSI co-doped spiro-OMeTAD. Moreover, benefiting from the improved ion migration barrier and hydrophobicity of the HTL, still retained nearly 80% of their initial power conversion efficiency after 36 days of exposure to ambient air.

Nuclear erythroid 2-related factor 2 protects against reactive oxygen species -induced preterm premature rupture of membranes through regulation of mitochondria†.

Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth and neonatal mortality. Reactive oxygen species (ROS) have been identified as a critical factor in the development of pPROM. Mitochondria are known to be the primary source of ROS and play a vital role in maintaining cellular function. The Nuclear erythroid 2-related factor 2 (NRF2) has been demonstrated to play a crucial role in regulating mitochondrial function. However, research exploring the impact of NRF2-regulated mitochondria on pPROM is limited. Therefore, we collected fetal membrane tissues from pPROM and spontaneous preterm labor (sPTL) puerpera, measured the expression level of NRF2, and evaluated the degree of mitochondrial damage in both groups. In addition, we isolated human amniotic epithelial cells (hAECs) from the fetal membranes and used small interfering RNA (siRNA) to suppress NRF2 expression, enabling us to evaluate the impact of NRF2 on mitochondrial damage and ROS production. Our findings indicated that the expression level of NRF2 in pPROM fetal membranes was significantly lower than in sPTL fetal membranes, accompanied by increased mitochondrial damage. Furthermore, after the inhibition of NRF2 in hAECs, the degree of mitochondrial damage was significantly exacerbated, along with a marked increase in both cellular and mitochondrial ROS levels. The regulation of the mitochondrial metabolic process via NRF2 in fetal membranes has the potential to influence ROS production.

Hepatitis E virus infection activates NOD-like receptor family pyrin domain-containing 3 inflammasome antagonizing interferon response but therapeutically targetable.

BACKGROUND AND AIMS: HEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting. APPROACH AND RESULTS: We measured IL-1ß secretion, the hallmark of inflammasome activation, in serum of HEV-infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte-derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL-1ß production. A profound increase of IL-1ß secretion was further observed in HEV-infected patients (1,733 ± 1,234 pg/mL; n = 70) compared to healthy persons (731 ± 701 pg/mL; n = 70). Given that macrophages are the drivers of inflammatory response, we found that inoculation with infectious HEV particles robustly triggered NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF-κB signaling activation as a key upstream event of HEV-induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibits HEV and inflammasome response without cross-interference. CONCLUSIONS: HEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting of NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.

Large steering range and low-loss integrated optical phased array with SiN-Si dual-layer non-uniform antenna.

We propose and demonstrate a 64-channel SiN-Si dual-layer optical phased array (OPA). By taking advantages of both SiN and Si materials, high-power handling and efficient modulation could be achieved simultaneously. In addition, steering range and emission loss are improved by introducing the non-uniform dual-layer antenna. Thinned array efficiently utilized in microwave phased array is first introduced to the OPA. Design details and the corresponding simulation results are presented, and the proposed OPA is successfully fabricated and experimentally characterized. 2D scanning with a steering range of 120°×13.9° and with a resolution of 0.052°×2.72° is demonstrated and a total loss of 12.66 dB is also measured, making it promising for high-resolution long-distance light detection and ranging (Lidar) applications.

Potential prognostic and therapeutic value of ANXA8 in renal cell carcinoma: based on the comprehensive analysis of annexins family.

BACKGROUND: Annexins are a family of proteins involved in a wide variety of cellular processes such as inflammation, proliferation, differentiation, apoptosis, migration and membrane repair. However, the role of most Annexins in renal cell carcinoma (RCC) remained unclear. METHODS: The differentially expressed Annexins in RCC compared with normal controls were screened applying the TCGA database. The correlation of differentially expressed Annexins with clinical stages, grades and overall survival was analyzed to explore the clinical significance of Annexins in RCC. Then ANXA8 was selected and further stained in the discover and validation RCC cohort. The correlation of ANXA8 expression with clinical parameter was verified at the protein level. To explore the potential function of ANXA8, ANXA8 was knockdown in the RCC cell line and further analyzed using transcriptome and bioinformatic analysis. RESULTS: mRNA expression of ANXA1, ANXA2R, ANXA4, ANXA8, ANXA8L1 and ANXA13 were significantly upregulated in RCC compared with normal kidney tissues. In contrast, ANXA3 and ANXA9 mRNA expression was significantly downregulated. Higher expression of ANXA2R, ANXA8 and ANXA8L1 were correlated with worse overall survival, while lower expression of ANXA3, ANXA9 and ANXA13 were associated with worse clinical outcomes in RCC patients. We further demonstrated that ANXA8 expression was significantly increased in RCC compared with normal renal tissues at the protein level. And higher protein expression of ANXA8 was associated with higher clinical grades. Through the bioinformatics analysis and cell cycle analysis, we found knockdown of ANXA8 mainly influenced the cell cycle and DNA replication. The top ten hub genes consist of CDC6, CDK2, CHEK1, CCNB1, ORC1, CHEK2, MCM7, CDK1, PCNA and MCM3. CONCLUSIONS: Multiple members of Annexins were abnormally expressed and associated with the prognosis of RCC. The expression of ANXA8 was significantly increased in RCC and associated with poor prognosis. ANXA8 might influence the cell cycle and could be a potential biomarker and therapeutic target for RCC.

Deciphering the Synergies of Reductive Soil Disinfestation Combined with Biochar and Antagonistic Microbial Inoculation in Cucumber Fusarium Wilt Suppression Through Rhizosphere Microbiota Structure.

Application of reductive soil disinfestation (RSD), biochar, and antagonistic microbes have become increasingly popular strategies in a microbiome-based approach to control soil-borne diseases. The combined effect of these remediation methods on the suppression of cucumber Fusarium wilt associated with microbiota reconstruction, however, is still unknown. In this study, we applied RSD treatment together with biochar and microbial application of Trichoderma and Bacillus spp. in Fusarium-diseased cucumbers to investigate their effects on wilt suppression, soil chemical changes, microbial abundances, and the rhizosphere communities. The results showed that initial RSD treatment followed by biochar amendment (RSD-BC) and combined applications of microbial inoculation and biochar (RSD-SQR-T37-BC) decreased nitrate concentration and raised soil pH, soil organic carbon (SOC), and ammonium in the treated soils. Under RSD, the applications of Bacillus (RSD-SQR), Trichoderma (RSD-T37), and biochar (RSD-BC) suppressed wilt incidence by 26.8%, 37.5%, and 32.5%, respectively, compared to non-RSD treatments. Moreover, RSD-SQR-T37-BC and RSD-T37 caused greater suppressiveness of Fusarium wilt and F. oxysporum by 57.0 and 33.5%, respectively. Rhizosphere beta diversity and alpha diversity revealed a difference between RSD-treated and non-RSD microbial groups. The significant increase in the abundance, richness, and diversity of bacteria, and the decrease in the abundance and diversity of fungi under RSD-induced treatments attributed to the general suppression. Identified bacterial (Bacillus, Pseudoxanthomonas, Flavobacterium, Flavisolibacter, and Arthrobacter) and fungal (Trichoderma, Chaetomium, Cladosporium, Psathyrella, and Westerdykella) genera were likely the potential antagonists of specific disease suppression for their significant increase of abundances under RSD-treated soils and high relative importance in linear models. This study infers that the RSD treatment induces potential synergies with biochar amendment and microbial applications, resulting in enhanced general-to-specific suppression mechanisms by changing the microbial community composition in the cucumber rhizosphere.

A novel near-infrared EGFR targeting probe for metastatic lymph node imaging in preclinical mouse models.

For the treatment of patients with oral squamous cell carcinoma (OSCC), the imaging of cervical lymph nodes and the evaluation of metastastic progression are of great significance. In recent years, the development of new non-radioactive lymph node tracers has been an area of intense research. Here, we report the synthesis, good biocompatibility, and in vivo evaluation of a new small molecule near-infrared (NIR) fluorescence probe by the conjugation of Lapatinib to S0456 (LP-S). We show that like Lapatinib, LP-S binds to the epidermal growth factor receptor (EGFR) resulting in high quality fluorescence imaging of metastatic lymph nodes in OSCC mouse models. After local injection of LP-S into the tumor, the lymphatic drainage pathway and lymph nodes can be clearly identified by NIR fluorescence imaging. Further, the LP-S probe shows higher contrast and longer retention in metastatic lymph nodes, allowing them to be differentiated from normal lymph nodes, and affording a new choice for fluorescence-guided surgery. Scheme. Chemical synthesis and application of EGFR targeting probe LP-S for imaging of metastatic lymph nodes (mLNs) in OSCC.