Factors Influencing Readiness for Hospital Discharge among Patients Undergoing Enterostomy: A Descriptive, Cross-sectional Study.

OBJECTIVE: To examine the factors influencing hospital discharge readiness among Chinese patients who have undergone enterostomy. METHODS: In this descriptive, cross-sectional study, researchers recruited patients with colorectal cancer who underwent enterostomy at a tertiary hospital in Guangdong Province, China, via convenience sampling between January 2021 and January 2023. Participants completed the Readiness for Hospital Discharge Scale, Ostomy Self-care Ability Scale, and Stoma-Quality of Life-Chinese Questionnaire (Chinese version) at the time of hospital discharge. Univariate, correlation, and multiple linear regression analyses were performed to explore the impact of self-care ability, quality of life, and other clinicodemographic characteristics on patients' readiness for hospital discharge. RESULTS: Of the 200 questionnaires distributed, 177 (88.5%) were completed and included in the final analysis. The median scores for the factors considered in this study were as follows: Readiness for Hospital Discharge Scale was 148.00 (interquartile range [IQR], 117.50, 164.00), self-care intention of the Ostomy Self-care Ability Scale was 36.00 (IQR, 34.00, 40.00), self-care knowledge of the Ostomy Self-care Ability Scale was 17.00 (IQR, 15.00, 19.00), self-care skill of the Ostomy Self-care Ability Scale was 5.00 (IQR, 3.00, 6.00), and the total score for quality of life was 60.00 (IQR, 49.00, 69.00). Multiple linear regression analysis identified several key factors explaining 48.2% of the variance in global readiness for hospital discharge: global quality of life (ß = .347, P < .001), self-care knowledge (ß = .259, P < .001), leakage during hospitalization (ß = -0.241, P < .001), monthly family income (ß = .148, P = .008), stoma siting before surgery (ß = .130, P = .020), and self-care intention (ß = .127, P = .035). CONCLUSIONS: The readiness for hospital discharge among patients undergoing enterostomy in this study was high. Factors such as quality of life, self-care knowledge, leakage during hospitalization, monthly family income, stoma siting before surgery, and self-care intention after undergoing enterostomy influenced the patients' readiness for hospital discharge. Therefore, future studies should focus on developing interventions to enhance patients' readiness for hospital discharge.

Developing NIR xanthene-chalcone fluorophores with large Stokes shifts for fluorescence imaging.

A series of novel near-infrared (NIR) xanthene-chalcone fluorophores were constructed through a modular synthesis with the electron-donating xanthene moiety and the electron-withdrawing chalcone moiety. These fluorophores are convenient for fluorescence imaging in living cells, benefiting from their NIR emissions (650-710 nm), large Stokes shifts (>100 nm), moderate quantum yields and low cytotoxicity. The substituted hydroxyl group of the xanthene-chalcone fluorophore HCA-E facilitates the development of multifunctional fluorescent probes. As an example, a highly sensitive and selective probe N-HCA-E for glutathione (GSH) detection was developed based on the fluorophore HCA-E. A 4-nitrobenzenesulfonyl (4-Ns) group was introduced to cage the hydroxyl group of HCA-E, which was used as a selective recognition site for the thiol of GSH and an effective fluorescence quencher. Probe N-HCA-E revealed NIR "turn-on" fluorescence (709 nm) for endogenous and exogenous GSH detection in lysosomes with a large Stokes shift (129 nm) and high anti-interference ability.

Fluorescent small molecule donors.

Small molecule donors (SMDs) play subtle roles in the signaling mechanism and disease treatments. While many excellent SMDs have been developed, dosage control, targeted delivery, spatiotemporal feedback, as well as the efficiency evaluation of small molecules are still key challenges. Accordingly, fluorescent small molecule donors (FSMDs) have emerged to meet these challenges. FSMDs enable controllable release and non-invasive real-time monitoring, providing significant advantages for drug development and clinical diagnosis. Integration of FSMDs with chemotherapeutic, photodynamic or photothermal properties can take full advantage of each mode to enhance therapeutic efficacy. Given the remarkable properties and the thriving development of FSMDs, we believe a review is needed to summarize the design, triggering strategies and tracking mechanisms of FSMDs. With this review, we compiled FSMDs for most small molecules (nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, reactive oxygen species and formaldehyde), and discuss recent progress concerning their molecular design, structural classification, mechanisms of generation, triggered release, structure-activity relationships, and the fluorescence response mechanism. Firstly, from the large number of fluorescent small molecular donors available, we have organized the common structures for producing different types of small molecules, providing a general strategy for the development of FSMDs. Secondly, we have classified FSMDs in terms of the respective donor types and fluorophore structures. Thirdly, we discuss the mechanisms and factors associated with the controlled release of small molecules and the regulation of the fluorescence responses, from which universal guidelines for optical properties and structure rearrangement were established, mainly involving light-controlled, enzyme-activated, reactive oxygen species-triggered, biothiol-triggered, single-electron reduction, click chemistry, and other triggering mechanisms. Fourthly, representative applications of FSMDs for trackable release, and evaluation monitoring, as well as for visible in vivo treatment are outlined, to illustrate the potential of FSMDs in drug screening and precision medicine. Finally, we discuss the opportunities and remaining challenges for the development of FSMDs for practical and clinical applications, which we anticipate will stimulate the attention of researchers in the diverse fields of chemistry, pharmacology, chemical biology and clinical chemistry. With this review, we hope to impart new understanding thereby enabling the rapid development of the next generation of FSMDs.

Effect of Orem's self-care model on discharge readiness of patients undergoing enterostomy: A randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of Orem's self-care model in preparing hospitals for the discharge of patients with colorectal cancer who undergo enterostomy. METHODS: 92 patients with enterostomy were recruited between February 2022 and February 2023 from a general tertiary hospital. The participants were assigned to either the intervention group or the control group randomly. The intervention group received Orem's self-care program and a three-month follow-up, whereas the control group received only routine care and a three-month follow-up. Discharge readiness, self-care ability, and stoma-quality-of-life data were collected at hospital discharge (T1), 30 days (T2), and 90 days (T3) after discharge. RESULTS: The intervention group had substantially higher discharge readiness (knowledge, p < 0.001; coping ability, p = 0.006; personal status, p = 0.001; expected support, p = 0.021; total score, p < 0.001), better self-care ability at T1 (self-care knowledge, p < 0.001; self-care skills, p = 0.010), better total quality of life (QoL) at T1, T2, and T3 (p < 0.001; p = 0.006; p = 0.014); better stoma management and daily routine at T1 (p = 0.004; p < 0.001); and better daily routine at T2 (p = 0.009) than the control group. CONCLUSIONS: The designed discharge readiness program based on Orem's self-care could promote effective patient discharge readiness, self-care knowledge, self-care skills, and QoL. TRIAL REGISTRATION: The trial number ChiCTR2200056302 registered on ClinicalTrials.gov.

Design, synthesis, and biological evaluation of first-in-class FABP1 inhibitors for the treatment of NASH.

The fatty acid-binding protein 1 (FABP1) is a fatty acid transporter protein that is considered as an emerging target for metabolic diseases. Despite forceful evidence that the inhibition of FABP1 is essential for ameliorating NASH, pharmacological control and validation of FABP1 are hindered by a lack of relevant inhibitors as pharmacological tool. Therefore, the development of effective FABP1 inhibitors is a current focus of research. Herein, we firstly reported the comprehensive structure-activity relationship (SAR) study of novel FABP1 inhibitors derived from high throughput screening of our in-house library, which resulting in the identification of the optimal compound 44 (IC50 = 4.46 ± 0.54 µM). Molecular docking studies revealed that 44 forms stable hydrogen bonds with amino acids around the active pocket of FABP1. Moreover, 44 alleviated the typical histological features of fatty liver in NASH mice, including steatosis, lobular inflammation, ballooning and fibrosis. Additionally, 44 has been demonstrated to have lipid metabolism regulating, anti-oxidative stress and hepatoprotective properties. This study might be provided a promising insight into the field of NASH and inspiration for the development of FABP1 inhibitors.

S-Shaped Helical Singlet Diradicaloid and Its Transformation to Circumchrysene via a Two-Stage Cyclization.

Polycyclic hydrocarbons with diradical and polyradical characters usually display unique reactivities in ring-cyclization reactions. However, such reactions are rarely used to construct π-extended polycyclic aromatic hydrocarbons. Here, we describe the synthesis of an S-shaped doubly helical singlet diradicaloid compound and its facile transformation into an unprecedented circumchrysene via a two-stage ring cyclization, which includes: (1) an eletrocylization from diradicaloid precursor and (2) a Scholl reaction. The reaction mechanism was investigated through in situ spectroscopic studies, assisted by theoretical calculations. This reaction sequence yields an optically resolved π-extended [5]helicene derivative with a fluorescence quantum yield up to 85% and a circularly polarized luminescence brightness up to 6.05 M-1 cm-1 in the far-red to near-infrared regions. This sequence also yielded a highly delocalized circumchrysene molecule, exhibiting large electron delocalization, moderate fluorescence quantum yield, and multistage redox properties.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

First report of basal stem rot caused by three Fusarium species on Chinese yam in China.

The cultivated variety of Chinese yam (Dioscorea polystachya Turcz. cv. Tiegun) is an economically important plant, capable of producing tubers that are used as food and traditional Chinese medicine. The basal stem rot was found on approximately 65% of yam (tuber expansion stage) in a total of 10 ha field in Wuzhi, Wen, and Hua counties, Henan, China (Sep 2021). Dark brown fusiform lesions initially occurred at the stems basal, irregularly extending to join together and leading to loop-stem necrotic indentation. Three diseased samples from Wuzhi county were collected, cut into 5 × 5 mm pieces, surface sterilized in 75% ethanol (30 s) and 1% NaClO (1 min), washed in sterile water 3 times, and placed on PDA in the dark for 3 days at 28℃. A total of 44 isolates forming three groups of Fusarium colonies were obtained using monosporic isolation, of which 19, 8, and 17 isolates were identified as F. oxysporum, F. solani, and F. proliferatum based on colony morphology, respectively. Typical isolates SYJJ6, 9, and 10 for each group were further studied. The SYJJ6 colonies showed gray white abundant fluffy aerial mycelium with rough edges, formation of ellipsoid, unicellular microconidia without septa, 5.6 to 13.4 × 2.4 to 4.7 µm (n = 50), and sickle-shaped, slightly curved macroconidia with 2 to 4 septa, 14.0 to 23.9 × 3.4 to 5.1 µm (n = 50). Isolate SYJJ9 produced flocculent white colonies, grew in a circular pattern with a sharp edge, forming oval or oblong microconidia with zero or one septum, 11.2 to 18.8 × 3.4 to 6.2 µm (n = 50), and slightly curved macroconidia with 2 to 3 septa, 27.6 to 44.0 × 3.9 to 7.4 µm (n = 50). SYJJ10 produced whitish or pinkish white colonies with fluffy aerial mycelium and a red pigmentation, produced renal or oval microconidia with no septa, 5.1 to 11.8 × 1.8 to 4.2 µm (n = 50), and falcate, slightly curved macroconidia with 3 to 4 septa, 16.1 to 30.2 × 3.1 to 5.9 µm (n = 50). Additionally, TUB, EF-1α, and RPB2 genes were amplified with primers BT2a/BT2b, EF1/EF2, and 5f2/-7cr, respectively (Glass and Donaldson 1995; O'Donnell et al. 1998, 2010). BLASTn analysis on SYJJ6 (OR047663, OR047666, OR047669), SYJJ9 (OR047665, OR047667, OR047670), and SYJJ10 (OR047664, OR047668, OR047671) gene sequences were over 99% identical to those of F. oxysporum (100%, MK432917; 100%, MN417196; 99.61%, MN457531), F. solani (100%, MF662662; 100%, MN223440; 99.80%, CP104055), and F. proliferatum (100%, ON557521; 100%, ON458137; 99.90%, LT841266), respectively. Pathogenicity tests of three isolates were separately performed on 60-day-old yam seedlings. The basal stems were wounded using needle, and the wounds were wrapped with cotton balls soaked with conidial suspension (1 mL, 3×106 conidia/mL) or water (control). Each isolate treated three plants and repeated three times. All plants were grown at 28℃ under a 16/8-h light/dark cycle. Typical symptoms emerged on basal stems at 16, 13, and 17 days after inoculation with the conidia of isolates SYJJ6, 9, and 10, while the control basal stems appeared healthy. The re-isolated fungi were identical to the original three isolates. Fusarium species (F. oxysporum, F. commune, F. humuli, etc.)were previously reported to cause wilt or stem rot on different D. polystachya cultivars (Fang et al. 2020; Li et al. 2023; Zhao et al. 2013), or basal stem rot on Panax ginseng (Ma et al. 2020). This is the first report of Chinese yam basal stem rot caused by Fusarium species, which threatens the production of Chinese yam 'Tiegun' and should be further studied.

A new perspective on structural characterisation and immunomodulatory activity of arabinogalactan in Larix kaempferi from Qinling Mountains.

In this study, crude polysaccharide (LAG-C) and homogeneous arabinogalactan (LAG-W) were isolated from Qinling Larix kaempferi of Shaanxi Province. Bioactivity assays showed that LAG-W and LAG-C enhanced the phagocytic ability, NO secretion, acid phosphatase activity, and cytokine production (IL-6, IL-1ß, and TNF-α) of RAW264.7 macrophages. Notably, LAG-W exhibited a significantly stronger immunomodulatory effect than LAG-C. The primary structure of LAG-W was characterised by chemical methods (monosaccharide composition, methylation analysis, and alkali treatment) and spectroscopic techniques (gas chromatography-mass spectrometry, high-performance liquid chromatography-mass spectrometry, and 1D/2D nuclear magnetic resonance). LAG-W was identified as a 22.08 kilodaltons (kDa) neutral polysaccharide composed of arabinose and galactose at a 1:7.5 molar ratio. Its backbone consisted of repeated →3)-ß-Galp-(1→ residues. Side chains, connected at the O-6 position, were mainly composed of T-ß-Galp-(1→ and T-ß-Galp-(1→6)-ß-Galp-(1→ residues. And it also contained small amounts of T-ß-Arap-(1→, T-α-Araf-(1→6)-ß-Galp-(1→6)-ß-Galp-(1→, and T-α-Araf-(1→3)-α-Araf-(1→6)-ß-Galp-(1→ residues. By structurally and functionally characterising L. kaempferi polysaccharides, this study opens the way for the valorisation of this species.

Microenvironment-differential Imaging of Demethylated Metabolites of Methionine for Identifying Ferroptosis Regional Preferences with Path-independent Equifinal Fluorescence Probes.

We realized the microenvironment-differential Imaging of demethylated metabolites of methionine and the regional regulation of ferroptosis.

Rapid quantification of grapeseed oil multiple adulterations using near-infrared spectroscopy coupled with a novel double ensemble modeling method.

As a high-quality edible oil, grapeseed oil is often adulterated with low-price/quality vegetable oils. A novel ensemble modeling method is proposed for quantitative analysis of grapeseed oil adulterations combined with near-infrared (NIR) spectroscopy. The method combines Monte Carlo (MC) sampling and whale optimization algorithm (WOA) to build numerous partial least squares (PLS) sub-models, named MC-WOA-PLS. A total of 80 adulterated grapeseed oil samples were prepared by mixing grapeseed oil with soybean oil, palm oil, cottonseed oil, and corn oil with the designed mass percentages. NIR spectra of the 80 samples were measured in a transmittance mode in the range of 12,000-4000 cm-1. Parameters in MC-WOA-PLS including the number of latent variables (LVs) in PLS, iteration number of WOA, whale number, number of PLS sub-models, and percentage of training subsets were optimized. To validate the prediction performance of the model, root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV), root mean squared error of prediction (RMSEP), correlation coefficient (R), residual predictive deviation (RPD), and standard deviation (S.D.) were used. Compared with PLS, standard normal variate-PLS (SNV-PLS), uninformative variable elimination-PLS (UVE-PLS), Monte Carlo uninformative variable elimination-PLS (MCUVE-PLS), randomization test-PLS (RT-PLS), variable importance in projection-PLS (VIP-PLS), and WOA-PLS, MC-WOA-PLS achieves the best prediction accuracy and stability for quantification of the five pure oils in adulterated grapeseed oil samples.

Integrated analysis of natural glycans using a versatile pyrazolone-type heterobifunctional tag ANPMP.

Glycans mediate various biological processes through carbohydrate-protein interactions, and glycan microarrays have become indispensable tools for understanding these mechanisms. However, advances in functional glycomics are hindered by the absence of convenient and universal methods for obtaining natural glycan libraries with diverse structures from glycoconjugates. To address this challenge, we have developed an integrative approach that enables one-pot release and simultaneously capture, separation, structural characterization, and functional analysis of N/O-glycans. Using this approach, glycoconjugates are incubated with a pyrazolone-type heterobifunctional tag-ANPMP to obtain glycan-2ANPMP conjugates, which are then converted to glycan-AEPMP conjugates. We prepared a tagged glycan library from porcine gastric mucin, soy protein, human milk oligosaccharides, etc. Following derivatization by N-acetylation and permethylation, glycans were subjected to detailed structural characterization by ESI-MSn analysis, which revealed >83 highly pure glycan-AEPMPs containing various natural glycan epitopes. A shotgun microarray is constructed to study the fine details of glycan-bindings by proteins and antisera.

Comparative Analysis of Free and Glycoconjugates Oligosaccharide Content in Milk from Different Species.

Human milk is important for infant growth, and oligosaccharides are one of its main functional nutrients. To enable a systematic comparison of free oligosaccharide and glycoconjugate content in milk from different species, the phenol-sulfuric acid and resorcinol assays were combined to determine the content. Using real samples, the method revealed that human milk contained the highest amount of total, neutral (9.84 ± 0.31 g/L), and sialylated (3.21 ± 0.11 g/L) free oligosaccharides, followed by goat milk, with neutral (0.135 ± 0.015 g/L) and sialylated (0.192 ± 0.016 g/L) free oligosaccharides and at a distance by bovine and yak milk. The highest total glycoconjugate content was detected in yak milk (0.798 ± 0.011 g/L), followed by human, bovine, and goat milk. These findings suggest that goat milk is the best source of free oligosaccharides in infant formula and functional dairy products and yak milk is the best source of glycoconjugates.

Impact of structurally diverse polysaccharides on colonic mucin O-glycosylation and gut microbiota.

Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of the colonic mucosa and gut microbiome were investigated in C57BL/6J mice fed six structurally diverse dietary polysaccharides and a mixture of six fibers. Dietary polysaccharides increased total O-glycans, mainly by stimulating neutral glycans. Highly branched arabinogalactan promoted terminally fucosylated core 1 O-glycans; whereas linear polysaccharides, including pectin, konjac glucomannan, inulin, and the fiber mixture, favored terminally di-fucosylated O-glycans. The last three polysaccharides also lowered the level of sulfated O-glycans and sialylated mono-fucosylated O-glycans. Varied monosaccharide composition in mixed polysaccharides had a synergistic beneficial effect, boosting fucosylated neutral glycans, decreasing acidic glycans, and stimulating microbial richness and diversity. Dietary polysaccharides containing arabinose and sulfate groups enhanced the relative abundances of Akkermansia and Muribaculaceae, respectively. The present comparison reveals the relationship between dietary polysaccharide structure, mucin O-glycan composition, and intestinal microorganisms.

Structure-activity strategies for mechanically responsive fluorescent materials: a molecular perspective.

Mechanical response luminescence (MRL) describes the photophysical properties triggered by mechanical stimulation. Usually, MRL can be regulated by intermolecular interactions, molecular conformation or molecular packing, to achieve the desirable optical properties. Herein, at the molecular level, this review covers the factors that influence mechanically responsive fluorescent materials, involving the single- or multifactorial modulation of aliphatic chains, donor-receptor switch, substituent adjustment, and position isomerism. According to these factors, the structure-activity strategies can be summarized as: (i) the self-recovery of optical properties, from the final to initial state, can be regulated by introducing long alkyl chains to a fluorophore. (ii) The sensitivity of MRL materials can be controlled by modifying the donor-acceptor structure via the changed ICT (intramolecular charge transfer) and intramolecular interaction. (iii) The electronic and steric effects of substituents can affect ICT and intermolecular interactions, thereby resulting in high quantum yield and high-contrast MRL materials via changing the molecular stacking of crystalline states. (iv) Intermolecular interaction is modulated by the position isomerism of the substituents, which results in switched molecular packing for the extended response toward a wide range of stimuli. It is anticipated that the molecular mechanisms of these structure-activity relationships will serve as a significant reference for developing novel, high contrast, recyclable mechanical response luminous materials.

Comprehensive Comparison of Bioactive N-Glycans among Seven Species of Livestock and Poultry Plasma Using a Relative Quantification Strategy.

Glycans have been proven to play special roles in keeping human health as a class of nutritional and bioactive ingredients in many food materials. However, their broad use in the food industry is hindered by the lack of comprehensive analytical methods for high-quality food glycomics studies and large-quantity raw materials for their production. This study focuses on structural identification and quantitative comparison of bioactive N-glycans in seven species of livestock and poultry plasma as potential natural glycan resources by a novel comprehensive relative quantification strategy based on stable isotope labeling with nondeuterated and deuterated 4-methyl-1-(2-hydrazino-2-oxoethyl)-pyridinium bromide (d0/d7-HMP) in combination with linkage-specific derivatization of sialic acid residues. Methodological validation of the method in terms of detection sensitivity, signal resolution, quantification linearity, precision, and accuracy on model neutral and complicated sialylated glycans demonstrated its advantages over the existing methods. Based on this method, a series of bioactive N-glycans were found in seven species of livestock and poultry plasma, and their differences in structure, abundance percentages, and relative contents of N-glycans were revealed, demonstrating their excellent applicability for comprehensive food glycomics analysis and great exploitation potential of these plasma samples as large-quantity raw materials in producing bioactive N-glycans for application in food and pharmaceutical industries.

First Report of Cercospora Leaf Spot Caused by Cercospora cf. flagellaris on Lonicera japonica Thunb. in Henan, China.

Honeysuckle flower (Lonicera japonica Thunb.) is a traditional Chinese medicinal plant. It is perennial and widely cultivated in China, Japan and Korea. From late August to October in 2021 and 2022, leaf spots symptoms were observed on L. japonica in different planting fields in Yuzhou, Yuanyang and Fenqiu districts, Henan province, China. The disease incidence was above 85% which reduce photosynthesis. Early disease symptoms appeared as small, circular to elliptical, brown spots on the leaves and later the lesions (1 to 5 mm × 1 to 4 mm) slowly developed yellow haloes. The different brown lesions seldom merge and form larger irregular lesions. Small fragments (3 to 5 mm) of leave tissue were excised from the lesion margins and surface-sterilized in 3% NaClO for 3 min, followed by three washes with sterile distilled water, and then placed on potato dextrose agar (PDA) and incubated at 25°C in the dark for 5 days. A total number of 8 cultures were obtained and purified by single-spore subcultures on PDA for morphological identification. The colonies on PDA were whitish to gray, with cottony aerial mycelium. Conidiophores were fasciculate, olivaceous brown, straight or geniculate, uniform in width, multiseptate, and ranged from 290 to 700 µm (560 µm on average, n = 20). Conidia were hyaline, slightly curved or straight, needle shaped, truncate at the base, and terminal at the tip, 3 to 17-septate, and measuring 150 to 240 µm (180 µm on average, n = 20). The morphological features were consistent with Cercospora cf. flagellaris Ellis & G. Martin (Groenewald et al. 2013). The genomic DNA was extracted using CTAB method. The nuclear ribosomal internal transcribed spacer region (ITS), portions of the actin (ACT), histone H3 (HIS3), and translation elongation factor 1-α (TEF1) genes were amplified using primers ITS1/ITS4 (Groenewald et al. 2013), ACT-512F/ACT-783R (Carbone and Kohn 1999), CYLH3F/CYLH3R (Crous et al. 2006), and EF1-728F/EF1-986R (Carbone and Kohn 1999). The resulting 537-bp ITS, 226-bp ACT, 410-bp HIS3, and 306-bp TEF1 sequences of isolate JDJ002 were deposited in GenBank (accession nos. OR492367, OR548247, OR548248 and OR548248, respectively). Sequence analysis revealed that ITS, ACT, HIS3 and TEF1α sequences exhibited ≥99% of identity with the ITS (KP896013), ACT(KP895965), HIS3(MK991295) and TEF1 (MN180408) sequences of C. cf. flagellaris, respectively. A pathogenicity test was conducted on healthy of L. japonica leaves. The healthy leaves pricked from L. japonica plants, rinsed in autoclaved distilled water three times and dried with distilled filter paper. Then twelve healthy leave were inoculated with a mycelial plug (0.4 cm diameter) harvested from the periphery of two week-old colony. As negative control, leaves inoculated with PDA medium plugs. Inoculated leaves were covered with plastic bags to maintain high relative humidity and incubated at 25°C in growth chamber. After 7 days, the inoculated leaves showed symptoms identical to those observed in the field under natural conditions, whereas negative control remained symptom-free. Re-isolation of the fungus from lesions on inoculated leaves confirmed that the causal agent was C. cf. flagellaris. Pathogenicity tests were repeated three times by the same methods with the same results. To our knowledge, this is the first report of C. cf. flagellaris except Cercospora rhamni Fack., Alternaria alternata, Corynespora cassiicola or Phomopsis sp. causing leave spots on L. japonica in China.

HP-LSP: A reference of land surface phenology from fused Harmonized Landsat and Sentinel-2 with PhenoCam data.

Land surface phenology (LSP) products are currently of large uncertainties due to cloud contaminations and other impacts in temporal satellite observations and they have been poorly validated because of the lack of spatially comparable ground measurements. This study provided a reference dataset of gap-free time series and phenological dates by fusing the Harmonized Landsat 8 and Sentinel-2 (HLS) observations with near-surface PhenoCam time series for 78 regions of 10 × 10 km2 across ecosystems in North America during 2019 and 2020. The HLS-PhenoCam LSP (HP-LSP) reference dataset at 30 m pixels is composed of: (1) 3-day synthetic gap-free EVI2 (two-band Enhanced Vegetation Index) time series that are physically meaningful to monitor the vegetation development across heterogeneous levels, train models (e.g., machine learning) for land surface mapping, and extract phenometrics from various methods; and (2) four key phenological dates (accuracy ≤5 days) that are spatially continuous and scalable, which are applicable to validate various satellite-based phenology products (e.g., global MODIS/VIIRS LSP), develop phenological models, and analyze climate impacts on terrestrial ecosystems.

Discovery of novel carboxylesterase 2 inhibitors for the treatment of delayed diarrhea and ulcerative colitis.

Human carboxylesterase 2 (hCES2) is an enzyme that metabolizes irinotecan to SN-38, a toxic metabolite considered a significant source of side effects (lethal delayed diarrhea). The hCES2 inhibitors could block the hydrolysis of irinotecan in the intestine and thus reduce the exposure of intestinal SN-38, which may alleviate irinotecan-associated diarrhea. However, existing hCES2 inhibitors (except loperamide) are not used in clinical applications due to lack of validity or acceptable safety. Therefore, developing more effective and safer drugs for treating delayed diarrhea is urgently needed. This study identified a lead compound 1 with a novel scaffold by high-throughput screening in our in-house library. After a comprehensive structure-activity relationship study, the optimal compound 24 was discovered as an efficient and highly selective hCES2 inhibitor (hCES2: IC50 = 6.72 µM; hCES1: IC50 > 100 µM). Further enzyme kinetics study indicated that compound 24 is a reversible inhibitor of hCES2 with competitive inhibition mode (Ki = 6.28 µM). The cell experiments showed that compound 24 could reduce the level of hCES2 in living cells (IC50 = 6.54 µM). The modeling study suggested that compound 24 fitted very well with the binding pocket of hCES2 by forming multiple interactions. Notably, compound 24 can effectively treat irinotecan-induced delayed diarrhea and DSS-induced ulcerative colitis, and its safety has also been verified in subtoxic studies. Based on the overall pharmacological and preliminary safety profiles, compound 24 is worthy of further evaluation as a novel agent for irinotecan-induced delayed diarrhea.

Liver-resident CD44hiCD27- γδT Cells Help to Protect Against Listeria monocytogenes Infection.

BACKGROUND & AIMS: Gamma delta (γδ) T cells are heterogeneous and functionally committed to producing interferon (IFN)-γ and interleukin (IL)-17. γδT cells are defined as tissue-resident lymphocytes in barrier tissues. Among them, IL-17-producing γδT cells are relatively abundant in the liver. However, a systematic and comprehensive understanding of the residency characteristics and function of hepatic IL-17A+ γδT cells is lacking. METHODS: We undertook a single-cell analysis of γδT17 cells derived from murine livers. A parabiosis model was used to assess tissue residency. Fluorescence-activated cell sorting and adoptive transfer experiments were used to investigate the response and protective role of liver-resident CD44hiCD27- γδT cells in Listeria monocytogenes infection. Transwell assay was used to assess the role of macrophages in the chemotaxis of liver-resident CD44hiCD27- γδT cells. RESULTS: We identified hepatic IL-17A-producing γδT cells as CD44hiCD27- γδT cells. They had tissue-resident characteristics and resided principally within the liver. Vγ6+ T cells also exhibited liver-resident features. Liver-resident CD44hiCD27- γδT cells had significantly increased proliferation capacity, and their proportion rapidly increased after infection. Some CD44hiCD27- γδT cells could produce IL-17A and IFN-γ simultaneously in response to Lm infection. Adoptive transfer of hepatic CD44hiCD27- γδT cells into Lm-infected TCRδ-/- mice led to markedly lower bacterial numbers in the liver. Hepatic macrophages promoted the migration and accumulation of liver-resident CD44hiCD27- γδT cells into infection sites. CONCLUSIONS: Liver-resident CD44hiCD27- γδT cells protect against Lm infection. Hepatic macrophages coordinate with liver-resident CD44hiCD27- γδT cells and contribute to the clearance of Lm at the early stage of infection corporately.