Alterations in amygdala subregions-Default mode network connectivity after treatment in patients with schizophrenia.

Disrupted connectivity in the default mode network (DMN) during resting-state functional MRI (rs-fMRI) is well-documented in schizophrenia (SCZ). The amygdala, a key component in the neurobiology of SCZ, comprises distinct subregions that may exert varying effects on the disorder. This study aimed to investigate variations in functional connectivity (FC) between distinct amygdala subregions and the DMN in SCZ individuals and explore the effects of treatment on these connections. Fifty-six SCZ patients and 51 healthy controls underwent FC analysis and questionnaire surveys during resting state. The amygdala was selected as the region of interest (ROI) and subdivided into four parts. Changes in FC were examined, and correlations between questionnaire scores and brain activity were explored. Pre-treatment, SCZ patients exhibited reduced FC between the amygdala and DMN compared to HCs. After treatment, significant differences persisted in the right medial amygdala, while other regions did not differ significantly from controls. In addition, PANSS scores positively correlated with FC between the Right Medial Amygdala and the left SMFC (r = .347, p = .009), while RBANS5A scores showed a positive correlation with FC between the Left Lateral Amygdala and the right MTG (rho = -.347, p = .009). The rsFC between the amygdala and the DMN plays a crucial role in the treatment mechanisms of SCZ. This could provide a promising predictive indicator for understanding the neural mechanisms behind treatment and symptomatic improvement.

Real-time detection and resection of sentinel lymph node metastasis in breast cancer through a rare earth nanoprobe based NIR-IIb fluorescence imaging.

Sentinel lymph node (SLN) biopsy is a commonly employed procedure for the routine assessment of axillary involvement in patients with breast cancer. Nevertheless, conventional SLN mapping cannot reliably distinguish the presence and absence of metastatic disease. Additionally, the complex anatomical structures and lymphatic drainage patterns surrounding tumor sites pose challenges to the sensitivity of the near-infrared fluorescence imaging with subcutaneously injected probes. To identifying the SLN metastases, we developed a novel nanoprobe for in vivo fluorescence imaging within the second near-infrared (NIR-II) range. This nanoprobe utilizes rare-earth nanoparticles (RENPs) to emit bright fluorescence at 1525 nm and is conjugated with tumor-targeted hyaluronic acid (HA) to facilitate the detection of metastatic SLN. Upon intravenous administration, RENPs@HA effectively migrated to SLNs and selectively entered metastatic breast tumor cells through CD44-mediated endocytosis. The RENPs@HA nanoprobes exhibited rapid accumulation in metastatic inguinal lymph nodes in mouse model, displaying a 5.8-fold-stronger fluorescence intensity to that observed in normal SLNs. Consequently, these nanoprobes effectively differentiate metastatic SLNs from normal SLNs. Importantly, the probes accurately detected micrometastases. These findings underscore the potential of RENPs@HA for real-time visualization and screening of SLNs metastasis.

Carbon Nanotube Support, Carbon Loricae and Oxygen Defect Co-Promoted Superior Activities and Excellent Durability of RuO2 Nanoparticles Towards the pH-Universal H2 Evolution.

This work reports a strategy that integrates the carbon nanotube (CNT) supporting, ultrathin carbon coating and oxygen defect generation to fabricate the RuO2 based catalysts toward the pH-universal hydrogen evolution reaction (HER) with high efficiencies. Specifically, the CNT supported RuO2 nanoparticles with ultrathin carbon loricae and rich oxygen vacancies at the surface (C@OV-RuO2/CNTs-325) have been synthesized. The C@OV-RuO2/CNTs-325 shows superior activities and excellent durability for the HER. It only requires overpotentials of 36.1, 18.0, and 19.3 mV to deliver -10 mA cm-2 in the acidic, neutral, and alkaline media, respectively. Its HER activities are comparable to that of the Pt/C in the acidic media but higher than those of the Pt/C in the neutral and alkaline media. The C@OV-RuO2/CNTs-325 shows excellent HER durability with no activity losses for > 500 h in the acidic, neutral or alkaline media at -250 mA cm-2. The density-functional-theory calculations indicate that the CNT supporting, the carbon coating, and the OVs can modulate the d-band centers of Ru, increasing the HER activities of C@OV-RuO2/CNTs-325, and stabilize the Ru atoms in the catalyst, increasing the durability of the C@OV-RuO2/CNTs-325. More interestingly, the C@OV-RuO2/CNTs-325 shows great potential for practical applications toward overall seawater splitting.

Cerebellar functional connectivity and its associated genes: A longitudinal study in drug-naive patients with obsessive-compulsive disorder.

The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD.

Potential correlations between abnormal homogeneity of default mode network and personality or lipid level in major depressive disorder.

BACKGROUND: Default mode network (DMN) is one of the most recognized resting-state networks in major depressive disorder (MDD). However, the homogeneity of this network in MDD remains incompletely explored. Therefore, this study aims to determine whether there is abnormal network homogeneity (NH) of the DMN in MDD patients. At the same time, correlations between clinical variables and brain functional connectivity are examined. METHODS: We enrolled 42 patients diagnosed with MDD and 42 HCs. A variety of clinical variables were collected, and data analysis was conducted using the NH and independent component analysis methods. RESULTS: The study shows that MDD patients have higher NH values in the left superior medial prefrontal cortex (MPFC) and left posterior cingulate cortex (PCC) compared to HCs. Additionally, there is a positive correlation between NH values of the left superior MPFC and Eysenck Personality Questionnaire values. NH values of the left PCC are positively linked to CHOL levels, LDL levels, and utilization scores. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: Our findings indicate the presence of abnormal DMN homogeneity in MDD, underscoring the significance of DMN in the pathophysiology of MDD. Simultaneously, the study provides preliminary evidence for the correlation between clinical variables and brain functional connectivity.

First report of leaf spot disease caused by Cladosporium pseudocladosporioides on Lonicera caerulea L. in Heilongjiang Province, China.

Blue honeysuckle (Lonicera caerulea L.) has contributed to maintaining the forest's ecological balance and remarkable frost-resistant abilities, helping it withstand extremely cold conditions (-46 °C) and a wide pH range (5 to 8) (Sharma and Lee 2021). Between September 2022 and September 2023, leaf spots were observed on approximately 30% of blue honeysuckle plants of the 'Lanjingling' cultivar grown in a 1.13 ha field in Da Hinggan Ling Prefecture (50.32° N, 124.13° E) in Heilongjiang Province, China. The leaves of the affected plants displayed black-colored spots. To identify the causal agents, 10 healthy and symptomatic leaves were randomly collected from ten healthy and infected individual plants, respectively. Small (3 to 4 mm) segments of the symptomatic tissues were immersed in 5% sodium hypochlorite (NaOCl) for 3 min, rinsed three times with sterile distilled water, dried in a paper towel, and plated on 9-cm Petri dishes containing potato dextrose agar (PDA). Ten fungal colonies developed on the PDA plates with an isolation frequency of 100% from 10 symptomatic leaves, and all colonies displayed a morphology consistent with Cladosporium spp. (Bensch et al. 2018). Cladosporium-like fungi were not isolated from healthy leaves. Dark olive-colored mycelia were observed, with straight unbranched conidiophores bearing terminal light brown-colored limoniform conidia (1.80 to 4.50 × 2.10 to 12.60 µm) and surrounded by a thin line of white mycelium (Delisle-Houde et al. 2024). To confirm this identification, PCR amplification of two representative strains LD-299 and LD-300 genomic DNA was performed with ITS1/ITS4 (White et al. 1990) and ACT512F/ACT783R (Carbone and Kohn 1999) primers. Basic local alignment search tool (BLAST) analyses of the National Center for Biotechnology Information database showed that sequences of the ITS (PP600316, PP600317) and ACT (PP624334, PP624335) all revealed 100% (493/493 nt, 493/493 nt; 181/181 nt, 181/181 nt) shared identity with Cladosporium pseudocladosporioides strain ex-type MF473195 and HM148674 (Bensch et al. 2010), respectively. Using a neighbor-joining phylogenetic analysis based on the ITS and ACT sequences, isolates LD-299 and LD-300 clustered in the same clade of C. pseudocladosporioides. Therefore, based on its morphological characteristics and molecular phylogeny, the two isolates were identified as C. pseudocladosporioides (Cosseboom and Hu 2023). A pathogenicity test was performed using nine healthy two-year-old blue honeysuckle Lanjingling plants. Three plants were inoculated with either the LD-299 or the LD-300 conidial suspension (1 × 106 spores/ml) or with clean water as an experimental control (Aydogdu et al. 2023). All plants were cultured in a greenhouse (28℃, 75% relative humidity, 12 h light and dark cycle), and each experiment was replicated three times. Typical leaf spot symptoms were first observed on the inoculated leaves after 10 days. Morphological and molecular characterization of re-isolated pathogens from the artificially infected leaves indicated that the two isolates were identical, thereby confirming Koch's postulates. Cladosporium pseudocladosporioides previously caused leaf spot disease on artichoke (Cynara scolymus) in Türkiye (Aydogdu et al. 2023). To the best of our knowledge, this is the first report of C. pseudocladosporioides causing leaf spots on blue honeysuckle in China. Blue honeysuckle production losses due to the leaf spots are critical for growers. Therefore, further focus should be given to investigate the host range and geographic distribution of C. pseudocladosporioides.

Association between the use of orexin receptor antagonists and falls or fractures: A meta-analysis.

Evidence indicates that the use of sedative-hypnotics, including benzodiazepines and z-drugs, is linked to an increased risk of falls and fractures. Nonetheless, the potential exacerbation of this risk by orexin receptor antagonists, which are novel therapeutic agents for treating insomnia, remains uncertain despite their escalating prevalence in clinical practice. We systematically searched four electronic databases from inception to April 17, 2024. In addition, we performed a quality assessment; calculated pooled odds ratios (ORs) to assess the relationship between the use of orexin receptor antagonists and the occurrence of falls or fractures; evaluated heterogeneity across the included studies; and conducted sensitivity analyses. The meta-analysis encompassed eight papers, comprising a total of 46,636 subjects. These papers included 5 case-control studies and 3 randomized controlled trials (RCTs), collectively encompassing ten studies. Analysis of the included case-control studies (pooled adjusted OR = 0.75, 95% confidence interval [CI] = 0.00-1.50, I2 = 66.2%, k = 3) and RCTs (OR = 0.68, 95% CI = 0.31-1.50, I2 = 45.9%, k = 5) indicated that the use of orexin receptor antagonists did not elevate the risk of falls. Similarly, analysis of the included case-control studies revealed no significant increase in the risk of fractures associated with the use of orexin receptor antagonists (pooled adjusted OR = 1.01, 95% CI = 0.82-1.20, I2 = 40.1%, k = 2). This meta-analysis suggests that the use of orexin receptor antagonists for treating insomnia does not escalate the risk of falls or fractures, although the data for lemborexant and daridorexant are limited.

Evaluation of Stripe Rust Resistance and Chip Detection Resistance Genes in 286 Xinjiang Wheat Cultivars and Breeding Lines.

Wheat stripe rust is a destructive disease worldwide, caused by Puccinia striiformis f. sp. tritici (Pst). Resistance breeding is the most effective method of controlling stripe rust. Xinjiang is a relatively independent epidemic region of wheat stripe rust in China. In recent years, wheat stripe rust in this area has shown an upward trend. Therefore, the purpose of this study was to evaluate the resistance level of wheat cultivars (lines) to the prevalent Pst races and determine the genetic background of stripe rust resistance genes in Xinjiang. Six predominant Pst races in China were used to study resistance of 286 wheat cultivars (lines) at both seedling under controlled conditions and adult-plant stages under field conditions. In the seedling tests, 175 (61.19%) entries were resistant to races CYR23, 125 (43.71%) to CYR29, 153 (53.50%) to CYR31, 88 (30.77%) to CYR32, 174 (60.84%) to CYR33, and 98 (34.27%) to CYR34. Among the resistant entries, 23 (8.04%) were resistant to all six races. In the field test, 135 (47.20%) entries were resistant to the tested mixed races. Through comparing the responses in the seedling and adult-plant stages, 109 (38.11%) entries were found to have adult-plant resistance (APR), and 14 (4.90%) entries have all-stage resistance (ASR). The 286 wheat entries were also tested using a wheat breeder chip containing 12 Yr resistance loci. Among these entries, 44 (15.38%) were found to have single gene, 221 (77.27%) have two or more genes, and 21 (7.34%) have none of the 12 genes, including 144 (50.35%) with Yr30 and 5 (1.75%) with YrSP. Entries with two or more genes have stronger resistance to Pst. Overall, the majority of entries have all-stage and/or adult-plant resistance, but their genes for resistance in addition to the 12 tested Yr genes need to be determined. It is also necessary to introduce more effective resistance genes in the breeding programs to improve stripe rust resistance in wheat cultivars in Xinjiang.

Potential correlations between asymmetric disruption of functional connectivity and metabolism in major depressive disorder.

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

First report of leaf spot disease caused by Pseudopithomyces chartarum on Lonicera caerulea L. in Heilongjiang Province, China.

Blue honeysuckle (Lonicera caerulea L.) cultivation has gradually expanded in China but continues to be limited by challenges such as leaf spot disease. Between September 2022 and September 2023, a leaf spot disease was observed on approximately 30% of 'Lanjingling' blue honeysuckles grown in a 2.66 ha field (a total of about 11,000 plants) in Jiamusi city (130.47°E, 46.16°N), Heilongjiang Province, China. Affected plants displayed brown necrotic lesions on their leaves that gradually expanded in area until the leaves fell off the plant entirely. Small, 3 to 4 mm segments of infected tissue from 50 randomly selected leaves were surface sterilized with 75% ethanol for 30 s and 5% sodium hypochlorite (NaOCl) for 3 min, rinsed three times with sterile distilled water, dried on paper towels, and plated in 9 cm Petri dishes containing potato dextrose agar (PDA) (Yan et al. 2022). Five pathogens (LD-232, LD-233, LD-234, LD-235, and LD-236) were isolated on PDA and displayed a conidia morphology consistent with Pseudopithomyces spp. (Perelló et al. 2017). The fungal colonies on PDA were villiform, white, and whorled and had sparse aerial mycelium on the surface with black conidiomata. The conidia were obpyriform and dark brown, had 0 to 3 transverse and 0 to 1 longitudinal septa, and measured 9.00 to 15.30 µm × 5.70 to 9.30 µm in size (n = 50). Genomic DNA was extracted from a representative isolate, LD-232, for molecular verification and PCR amplification was performed with ITS1/ITS4 (White et al. 1990), LROR/LR7 (Carbone and Kohn 1999), and RPB2-5F2/RPB2-7CR (Liu et al. 1999) primers. Sequences of LD-232 ITS (OR835654), LSU (OR835652), and RPB2 (OR859769) revealed 99.8% (530/531 nt), 98.8% (639/647 nt), and 99.8% (1015/1017 nt) shared identity with Pseudopithomyces chartarum sequences (OP269600, OP237014, and MK434892), respectively (Wu et al. 2023). Bayesian inference (BI) was used to construct the phylogenies using Mr. Bayes v. 3.2.7 to confirm the identity of the isolates (Ariyawansa et al. 2015). Phylogenetic trees cannot be constructed based on the genes' concatenated sequences because selective strains do not have complete rDNA-ITS, LSU, and RPB2 sequences. Therefore, based on the morphological characteristics and molecular phylogeny, LD-232 was identified as P. chartarum (Perelló et al. 2017; Wu et al. 2023). A pathogenicity test was performed with six healthy, two-year-old 'Lanjingling' blue honeysuckle plants. Three plants were inoculated by spraying the LD-232 conidial suspension (1 × 106 spores/ml) or clean water as an experimental control condition (Wu et al. 2023; Yan et al. 2023). All plants were cultured in a greenhouse at 28℃ under a 12-h light/dark cycle, and each experiment was replicated three times. Typical leaf spot symptoms were observed on inoculated leaves after 10 days. The same pathogens were reisolated from infected leaves, displayed the same morphological and molecular traits, and were again identified as P. chartarum, confirming Koch's postulate. P. chartarum previously caused leaf spot disease on Tetrapanax papyrifer in China (Wu et al. 2023). To our knowledge, this is the first report of blue honeysuckle leaf spot caused by P. chartarum in China. Identification of P. chartarum as a disease agent on blue honeysuckle will help guide future management of leaf diseases for this economically important small fruit tree.

First report of leaf spot disease caused by Neopestalotiopsis rosae on Lonicera caerulea L. in Heilongjiang Province, China.

Recently, interest in cultivating blue honeysuckle (Lonicera caerulea L.) for horticulture and medicinal uses has grown (Sharma and Lee 2021). Between September 2022 and September 2023, a leaf spot disease (Fig. S1) was observed on approximately 20% of 'Lanjingling' blue honeysuckles grown in a 0.18 ha field in Qiqihar city (123.43°E, 47.92°N), Heilongjiang Province, China. Infected plants displayed black leaf spots that expanded to cover the entire leaf. Small, 3 to 4 mm segments of infected tissue were surface sterilized with 75% ethanol for 30 s and 5% sodium hypochlorite (NaOCl) for 3 min, rinsed three times with sterile distilled water, dried on paper towels, and plated in 9 cm Petri dishes containing potato dextrose agar (PDA) (Ma et al. 2023). To induce sporulation, nine purified cultures (Fig. S2) with similar culture characteristics were finally obtained from ten infected plants and they displayed a conidia morphology consistent with Neopestalotiopsis spp., no other fungi were isolated, and the isolation frequency was 90%. Conidiomata (Fig. S3) were brown to black and distributed in concentric rings with an average size of 261.98 (60.30-451.80) µm (n = 50). The conidia (Fig. S3) were fusoid and had four septa, straight to slightly curved, with an average size of 23.48 (13.50-30.30) × 5.42 (4.50-9.30) µm(n = 50), while basal and apical cells were hyaline and the three middle cells were brown with darker septa. PCR amplification was performed with ITS1/ITS4 (White et al. 1990), EFl-728F/EF1-986R (Carbone and Kohn 1999), and Btub2Fd/Btub4Rd (Glass and Donaldson 1995) primers from the genomic DNA of the LD-330. Sequences of ITS (PP033584), TEF (PP048757), and TUB (PP048758) revealed 99 to 100% (499/500, 255/255, and 481/486) shared identity with Neopestalotiopsis rosae sequences (NR145243, KM199524, and KM199430) (Rebollar-Alviter et al. 2020). Therefore, based on morphological characteristics and molecular phylogeny, LD-330 was identified as N. rosae. Six two-year-old healthy plants of the 'Lanjingling' cultivar were selected for a pathogenicity test (Yan et al. 2023). The leaves were surface disinfected with 75% alcohol and then wiped with sterilized water three times. Three plants were inoculated with 10 ml of LD-330 conidial suspension (1 × 106 spores/ml) or with sterile water as an experimental control, respectively. All plants were in closed plastic bag, incubated in a greenhouse at 28 ℃ and 75% relative humidity (RH) under a 12-h light/dark cycle, and each experiment was performed three times (Rebollar-Alviter et al. 2020). Typical leaf spot symptoms were observed on inoculated leaves after 14 days (Fig. S4), whereas no symptoms were detected on water-treated leaves. The same pathogen was reisolated from infected leaves, displayed the same morphological and molecular traits, and was again identified as N. rosae, confirming Koch's postulate. Neopestalotiopsis rosae was previously reported on pecan (Gao et al. 2022), causing black leaf spot disease in China. To our knowledge, this is the first report of a blue honeysuckle leaf spot caused by N. rosae in China and specifically in the Heilongjiang province which has the largest blue honeysuckle cultivation area in the country. Future research should be directed toward developing comprehensive management measures.

Fractional amplitude of low-frequency fluctuations in sensory-motor networks and limbic system as a potential predictor of treatment response in patients with schizophrenia.

BACKGROUND: Previous investigations have revealed substantial differences in neuroimaging characteristics between healthy controls (HCs) and individuals diagnosed with schizophrenia (SCZ). However, we are not entirely sure how brain activity links to symptoms in schizophrenia, and there is a need for reliable brain imaging markers for treatment prediction. METHODS: In this longitudinal study, we examined 56 individuals diagnosed with 56 SCZ and 51 HCs. The SCZ patients underwent a three-month course of antipsychotic treatment. We employed resting-state functional magnetic resonance imaging (fMRI) along with fractional Amplitude of Low Frequency Fluctuations (fALFF) and support vector regression (SVR) methods for data acquisition and subsequent analysis. RESULTS: In this study, we initially noted lower fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, coupled with higher fALFF values in the left hippocampus and right putamen in SCZ patients compared to the HCs at baseline. However, when comparing fALFF values in brain regions with abnormal baseline fALFF values for SCZ patients who completed the follow-up, no significant differences in fALFF values were observed after 3 months of treatment compared to baseline data. The fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, and the left postcentral gyrus were useful in predicting treatment effects. CONCLUSION: Our findings suggest that reduced fALFF values in the sensory-motor networks and increased fALFF values in the limbic system may constitute distinctive neurobiological features in SCZ patients. These findings may serve as potential neuroimaging markers for the prognosis of SCZ patients.

A Dual-Cascade Activatable Near-Infrared Fluorescent Probe for Precise Intraoperative Imaging of Tumor.

Accurate intraoperative tumor delineation is critical to achieving successful surgical outcomes. However, conventional techniques typically suffer from poor specificity and low sensitivity and are time-consuming, which greatly affects intraoperative decision-making. Here, we report a cascade activatable near-infrared fluorescent (NIRF) probe IR780SS@CaP that can sequentially respond to tumor acidity and elevated glutathione levels for accurate intraoperative tumor localization. Compared with nonactivatable and single-factor activatable probes, IR780SS@CaP with a cascade strategy can minimize nonspecific activation and false positive signals in a complicated biological environment, affording a superior tumor-to-normal tissue ratio to facilitate the delineation of abdominal metastases. Small metastatic lesions that were less than 1 mm in diameter can be precisely identified by IR780SS@CaP and completely excised under NIRF imaging guidance. This study could benefit tumor diagnosis and image-guided tumor surgery by providing real-time information and reliable decision support, thus reducing the risk of both recurrence and complications to improve patient outcomes.

Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.

Improved fluorescence-based assay for rapid screening and evaluation of SARS-CoV-2 main protease inhibitors.

The outbreak of coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health. In parallel with vaccines, efficacious antivirals are urgently needed. SARS-CoV-2 main protease (Mpro) is an attractive drug target for antiviral development owing to its key roles in virus replication and host immune evasion. Due to the limitations of currently available methods, the development of novel high-throughput screening assays is of the highest importance for the discovery of Mpro inhibitors. In this study, we first developed an improved fluorescence-based assay for rapid screening of Mpro inhibitors from an anti-infection compound library using a versatile dimerization-dependent red fluorescent protein (ddRFP) biosensor. Utilizing this assay, we identified MG-101 as a competitive Mpro inhibitor in vitro. Moreover, our results revealed that ensitrelvir is a potent Mpro inhibitor, but baicalein, chloroquine, ebselen, echinatin, and silibinin are not. Therefore, this robust ddRFP assay provides a faithful avenue for rapid screening and evaluation of Mpro inhibitors to fight against COVID-19.

[Preparation and characterization of a fluorogenic ddRFP-M biosensor as a specific SARS-CoV-2 main protease substrate].

The conventional peptide substrates of SARS-CoV-2 main protease (Mpro) are frequently associated with high cost, unstable kinetics, and multistep synthesis. Hence, there is an urgent need to design affordable and stable Mpro substrates for pharmacological research. Herein, we designed a functional Mpro substrate based on a dimerization-dependent red fluorescent protein (ddRFP) for the evaluation of Mpro inhibitors in vitro. The codon-optimized DNA fragment encoding RFP-A1 domain, a polypeptide linker containing Mpro cleavage sequence (AVLQS), and the RFP-B1 domain was subcloned into the pET-28a vector. After transformation into Escherichia coli Rosetta(DE3) cells, the kanamycin resistant transformants were selected. Using a low temperature induction strategy, most of the target proteins (ddRFP-M) presented in the supernatant fractions were collected and purified by a HisTrapTM chelating column. Subsequently, the inhibition of Mpro by ensitrelvir and baicalein was assessed using ddRFP-M assay, and the biochemical properties of ddRFP-M substrate were analyzed. Our results showed that the fluorogenic substrate ddRFP-M was successfully prepared from E. coli cells, and this biosensor exhibited the expected specificity, sensitivity, and reliability. In conclusion, the production of the fluorogenic substrate ddRFP-M provides an expedient avenue for the assessment of Mpro inhibitors in vitro.

Altered interhemispheric functional connectivity in patients with obsessive-compulsive disorder and its potential in therapeutic response prediction.

The trajectory of voxel-mirrored homotopic connectivity (VMHC) after medical treatment in obsessive-compulsive disorder (OCD) and its value in prediction of treatment response remains unclear. This study aimed to investigate the pathophysiological mechanism of OCD, as well as biomarkers for prediction of pharmacological efficacy. Medication-free patients with OCD and healthy controls (HCs) underwent magnetic resonance imaging. The patients were scanned again after a 4-week treatment with paroxetine. The acquired data were subjected to VMHC, support vector regression (SVR), and correlation analyses. Compared with HCs (36 subjects), patients with OCD (34 subjects after excluding two subjects with excessive head movement) exhibited significantly lower VMHC in the bilateral superior parietal lobule (SPL), postcentral gyrus, and calcarine cortex, and VMHC in the postcentral gyrus was positively correlated with cognitive function. After treatment, the patients showed increased VMHC in the bilateral posterior cingulate cortex/precuneus (PCC/PCu) with the improvement of symptoms. SVR results showed that VMHC in the postcentral gyrus at baseline could aid to predict a change in the scores of OCD scales. This study revealed that SPL, postcentral gyrus, and calcarine cortex participate in the pathophysiological mechanism of OCD while PCC/PCu participate in the pharmacological mechanism. VMHC in the postcentral gyrus is a potential predictive biomarker of the treatment effects in OCD.

Evaluation of natural products from virtual screenings as SARS-CoV-2 main protease inhibitors using combinational experiments.

Recently, andrographolide, kaempferol, maslinic acid, rutin, and schaftoside have been identified as potent SARS-CoV-2 main protease (Mpro) inhibitors via molecular docking studies. However, no comprehensive in vitro testing of these compounds against Mpro has been conducted. In this study, we rigorously evaluated the in vitro inhibition of Mpro by these compounds using combinational experiments, including fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data revealed that these compounds are not Mpro inhibitors based on the results from a set of in vitro assays. These results suggest that an efficient combination of a molecular docking approach and an experimental assay is essential for the discovery of Mpro inhibitors in the future.