Ion Pairing Enables Targeted Prodrug Activation via Red Light Photocatalysis: A Proof-of-Concept Study with Anticancer Gold Complexes.

Photocatalysis has found increasing applications in biological systems, for example, in localized prodrug activation; however, high-energy light is usually required without giving sufficient efficiency and target selectivity. In this work, we report that ion pairing between photocatalysts and prodrugs can significantly improve the photoactivation efficiency and enable tumor-targeted activation by red light. This is exemplified by a gold-based prodrug (1d) functionalized with a morpholine moiety. Such a modification causes 1d to hydrolyze in aqueous solution, forming a cationic species that tightly interacts with anionic photosensitizers including Eosin Y (EY) and Rose Bengal (RB), along with a significant bathochromic shift of absorption tailing to the far-red region. As a result, a high photoactivation efficiency of 1d by EY or RB under low-energy light was found, leading to an effective release of active gold species in living cells, as monitored by a gold-specific biosensor (GolS-mCherry). Importantly, the morpholine moiety, with pKa ∼6.9, in 1d brings in a highly pH-sensitive and preferential ionic interaction under a slightly acidic condition over the normal physiological pH, enabling tumor-targeted prodrug activation by red light irradiation in vitro and in vivo. Since a similar absorption change was found in other morpholine/amine-containing clinic drugs, photocages, and precursors of reactive labeling intermediates, it is believed that the ion-pairing strategy could be extended for targeted activation of different prodrugs and for mapping of an acidic microenvironment by low-energy light.

The catabolic specialization of the marine bacterium Polaribacter sp. Q13 to red algal ß1,3/1,4-mixed-linkage xylan.

Catabolism of algal polysaccharides by marine bacteria is a significant process of marine carbon cycling. ß1,3/1,4-Mixed-linkage xylan (MLX) is a class of xylan in the ocean, widely present in the cell walls of red algae. However, the catabolic mechanism of MLX by marine bacteria remains elusive. Recently, we found that a marine Bacteroidetes strain, Polaribacter sp. Q13, is a specialist in degrading MLX, which secretes a novel MLX-specific xylanase. Here, the catabolic specialization of strain Q13 to MLX was studied by multiomics and biochemical analyses. Strain Q13 catabolizes MLX with a canonical starch utilization system (Sus), which is encoded by a single xylan utilization locus, XUL-Q13. In this system, the cell surface glycan-binding protein SGBP-B captures MLX specifically, contributing to the catabolic specificity. The xylanolytic enzyme system of strain Q13 is unique, and the enzymatic cascade dedicates the stepwise hydrolysis of the ß1,3- and ß1,4-linkages in MLX in the extracellular, periplasmic, and cytoplasmic spaces. Bioinformatics analysis and growth observation suggest that other marine Bacteroidetes strains harboring homologous MLX utilization loci also preferentially utilize MLX. These results reveal the catabolic specialization of MLX degradation by marine Bacteroidetes, leading to a better understanding of the degradation and recycling of MLX driven by marine bacteria.IMPORTANCERed algae contribute substantially to the primary production in marine ecosystems. The catabolism of red algal polysaccharides by marine bacteria is important for marine carbon cycling. Mixed-linkage ß1,3/1,4-xylan (MLX, distinct from hetero-ß1,4-xylans from terrestrial plants) is an abundant red algal polysaccharide, whose mechanism of catabolism by marine bacteria, however, remains largely unknown. This study reveals the catabolism of MLX by marine Bacteroidetes, promoting our understanding of the degradation and utilization of algal polysaccharides by marine bacteria. This study also sets a foundation for the biomass conversion of MLX.

Metagenomic analysis revealed the potential of lactic acid bacteria in improving natural saline-alkali land.

Management and improving saline-alkali land is necessary for sustainable agricultural development. We conducted a field experiment to investigate the effects of spraying lactic acid bacteria (LAB) on the cucumber and tomato plant soils. Three treatments were designed, including spraying of water, viable or sterilized LAB preparations to the soils of cucumber and tomato plants every 20 days. Spraying sterilized or viable LAB could reduce the soil pH, with a more obvious effect by using viable LAB, particularly after multiple applications. Metagenomic sequencing revealed that the soil microbiota in LAB-treated groups had higher alpha-diversity and more nitrogen-fixing bacteria compared with the water-treated groups. Both viable and sterilized LAB, but not water application, increased the complexity of the soil microbiota interactive network. The LAB-treated subgroups were enriched in some KEGG pathways compared with water or sterilized LAB subgroups, such as environmental information processing-related pathways in cucumber plant; and metabolism-related pathways in tomato plant, respectively. Redundancy analysis revealed association between some soil physico-chemical parameters (namely soil pH and total nitrogen) and bacterial biomarkers (namely Rhodocyclaceae, Pseudomonadaceae, Gemmatimonadaceae, and Nitrosomonadales). Our study demonstrated that LAB is a suitable strategy for decreasing soil pH and improving the microbial communities in saline-alkali land.

Comparative molecular dynamics simulations provided insights into the mechanisms of cold-adaption of alginate lyases from the PL7 family.

Alginate is an important polysaccharide that is abundant in the marine environments, including the Polar Regions, and bacterial alginate lyases play key roles in its degradation. Many reported alginate lyases show characteristics of cold-adapted enzymes, including relatively low temperature optimum of activities (Topt) and low thermal stabilities. However, the cold-adaption mechanisms of alginate lyases remain unclear. Here, we studied the cold-adaptation mechanisms of alginate lyases by comparing four members of the PL7 family from different environments: AlyC3 from the Arctic ocean (Psychromonas sp. C-3), AlyA1 from the temperate ocean (Zobellia galactanivorans), PA1167 from the human pathogen (Pseudomonas aeruginosa PAO1), and AlyQ from the tropic ocean (Persicobacter sp. CCB-QB2). Sequence comparison and comparative molecular dynamics (MD) simulations revealed two main strategies of cold adaptation. First, the Arctic AlyC3 and temperate AlyA1 increased the flexibility of the loops close to the catalytic center by introducing insertions at these loops. Second, the Arctic AlyC3 increased the electrostatic attractions with the negatively charged substrate by introducing a high portion of positively charged lysine at three of the insertions mentioned above. Furthermore, our study also revealed that the root mean square fluctuation (RMSF) increased greatly when the temperature was increased to Topt or higher, suggesting the RMSF increase temperature as a potential indicator of the cold adaptation level of the PL7 family. This study provided new insights into the cold-adaptation mechanisms of bacterial alginate lyases and the marine carbon cycling at low temperatures.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

[Application of process analysis technology in traditional Chinese medicine manufacturing industry].

In the traditional Chinese medicine(TCM) manufacturing industry, quality control determines the safety, effectiveness, and quality stability of the final product. The traditional quality control method generally carries out sampling off-line testing of drugs after the end of the batch production, which is incomprehensive, and it fails to find the problems in the production process in time. Process analysis technology(PAT) uses process testing, mathematical modeling, data analysis, and other technologies to collect, analyze, feedback, control, and continuously improve the critical quality attributes(CQA) in all aspects of the production of TCM preparations in real time. The application of PAT in the TCM manufacturing industry is one of the research hotspots in recent years, which has the advantages of real-time, systematic, non-destructive, green, and rapid detection for the production quality control of TCM preparations. It can effectively ensure the stability of the quality of TCM preparations, improve production efficiency, and play a key role in the study of the quantity and quality transfer law of TCM. Commonly used PAT includes near-infrared spectroscopy, Raman spectroscopy, online microwave, etc. In addition, the establishment of an online detection model by PAT is the key basic work to realize intelligent manufacturing in TCM production. Obtaining real-time online detection data through PAT and establishing a closed-loop control model on this basis are a key common technical difficulty in the industry. This paper adopted systematic literature analysis to summarize the relevant Chinese and foreign literature, policies and regulations, and production applications, and it introduced the development trend and practical application of PAT, so as to provide references for accelerating the application of PAT in the TCM manufacturing industry, the intelligent transformation and upgrading, and high-quality development of the TCM industry.

Screening of candidate genes related to differences in growth and development between Chinese indigenous and Western pig breeds.

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.

Multi-derivative method for phase extraction without knowing carrier frequencies in off-axis quantitative phase imaging.

We propose a multi-derivative method to reconstruct the phase of transparent objects in off-axis quantitative phase imaging (QPI). By numerically computing first-, second-, and third-order derivatives of the interferogram, we demonstrate that one can extract the quantitative phase information in a straightforward way, without prior knowledge of the carrier frequencies or Fourier transform. In contrast to existing advanced derivative methods, our approach markedly streamlines the alignment and retrieval processes, all without requiring any special prerequisites. This enhancement seamlessly translates into improved reconstruction quality. Furthermore, when compared to cutting-edge Fourier-division-based methods, our technique distinctly accelerates the phase retrieval speed. We verified our method using white-light diffraction phase microscopy and laser off-axis QPI, and the results indicate that our method can allow a fast, high-quality retrieval with frame rates up to 41.6 fps for one- megapixel interferograms on a regular computer.

Prognostic value of platelet distribution width to lymphocyte ratio in patients with hepatocellular carcinoma following hepatectomy.

BACKGROUND: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. RESULTS: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. CONCLUSION: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment.

The intricate symbiotic relationship between lactic acid bacterial starters in the milk fermentation ecosystem.

Fermentation is one of the most effective methods of food preservation. Since ancient times, food has been fermented using lactic acid bacteria (LAB). Fermented milk is a very intricate fermentation ecosystem, and the microbial metabolism of fermented milk largely determines its metabolic properties. The two most frequently used dairy starter strains are Streptococcus thermophilus (S. thermophilus) and Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus). To enhance both the culture growth rate and the flavor and quality of the fermented milk, it has long been customary to combine S. thermophilus and L. bulgaricus in milk fermentation due to their mutually beneficial and symbiotic relationship. On the one hand, the symbiotic relationship is reflected by the nutrient co-dependence of the two microbes at the metabolic level. On the other hand, more complex interaction mechanisms, such as quorum sensing between cells, are involved. This review summarizes the application of LAB in fermented dairy products and discusses the symbiotic mechanisms and interactions of milk LAB starter strains from the perspective of nutrient supply and intra- and interspecific quorum sensing. This review provides updated information and knowledge on microbial interactions in a fermented milk ecosystem.

The symbiotic relationship between Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus is reviewed.Their nutrient co-dependence is discussed.The role of quorum sensing in their interaction is discussed for the first time.This review is of interest to colleagues interested in exploiting LAB starter cultures.

Synergy-based functional electrical stimulation and robotic-assisted for retraining reach-to-grasp in stroke: a study protocol for a randomized controlled trial.

BACKGROUND: Stroke survivors have long-term upper limb impairment, which impacts the quality of life (QOL) and social reintegration, but there is lack of effective therapeutic strategies and novel technologies. Customized multi-muscle functional electrical stimulation (FES) based on the muscle synergy of healthy adults and robotic-assisted therapy (RAT) have been proved efficacy respectively. Synergy-based FES combined with RAT can be a novel and more effective therapy for upper limb recovery of stroke survivors from the perspective of synergistic enhancement. However, few studies have examined the effectiveness of combined synergy-based FES and RAT, especially for motor control evaluated by reach-to-grasp (RTG) movements. The main objective of the following research protocol is to evaluate the effectiveness and efficacy, as well as adoptability, of FES-RAT and FES or RAT rehabilitation program for upper limb function improvement after stroke. METHODS: This will be an assessor-blinded randomized controlled trial involving a 12-week intervention and a 6-month follow-up. Stratified randomization will be used to equally and randomly assign 162 stroke patients into the FES + conventional rehabilitation program (CRP) group, RAT + CRP group and FES-RAT + CRP group. Interventions will be provided in 5 sessions per week, with a total of 60 sessions. The primary outcome measurements will include the Fugl-Meyer Assessment and Biomechanical Assessment of RTG movements. The secondary outcome measurements will include quality of life and brain neuroplasticity assessments by MRI. Evaluations will be performed at five time points, including at baseline, 6 weeks and 12 weeks from the start of treatment, and 3 months and 6 months following the end of treatment. A two-way analysis of variance with repeated measures will be applied to examine the main effects of the group, the time factor and group-time interaction effects. DISCUSSION: The results of the study protocol will provide high quality evidence for integrated synergy-based FES and RAT, and synergy-based FES alone and guide the design of more effective treatment methods for stroke rehabilitation. TRIAL REGISTRATION: ChiCTR2300071588.

Atomic charges in molecules defined by molecular real space partition into atomic subspaces.

Atomic charge (AC), which is the charge distribution of a molecule, is an important property that is closely associated with structures, reactivities, and intra- and inter-molecular interactions among molecules. Several theoretical models or methods can be used to obtain the magnitudes of AC with different characteristics. These models can be classified into fuzzy-atoms models and models partitioning a molecule into individual atoms with sharp boundaries. The first category includes Mulliken, natural population analysis (NPA), Hirshfeld, Merz-Kollman-Singh (MK), CHELPG, the electronegativity equalization method (EEM), the atom-bond electronegativity equalization method (ABEEM), and atomic polar tensor (APT). The second category is derived from quantum chemical topology (QCT) and includes the quantum theory of atoms in molecules (QTAIM) and QCT analysis based on the potential acting on one electron in a molecule (PAEMQCT). Herein, after giving a bird's-eye view of the population methods of the first category, we specifically describe some features of the second category. We only present the basic framework of QCT for obtaining ACs from QTAIM and PAEMQCT and show their important characteristics. QCT establishes the basis of the following chemical concept: a molecule is spatially partitioned into individual atoms with sharp boundaries. The ACs from QTAIM are close to the atomic valence in chemistry, and ACs from PAEMQCT may be practically suitable for modeling intra- and inter-molecular interactions.

Development of a QM/MM(ABEEM) method combined with a polarizable force field to investigate the excision reaction mechanism of damaged thymine.

This paper focuses on the development of a quantum mechanics/molecular mechanics method using the ABEEM polarizable force field (QM/MM(ABEEM) method) to investigate the excision reaction mechanism of damaged thymine. This method does not simply combine the QM method with the polarizable force field. A valence electronegativity piecewise function with the distance between atoms as a variable is introduced to describe the atomic partial charges, and changes greatly during the reaction process. At the same time, the charge transfer effect is treated using the condition of local charge conservation. Compared with the traditional QM/MM method, the QM/MM(ABEEM) method can more accurately simulate the polarization effect and charge transfer effect in the reaction process. Focusing on the controversial problems of the excision of damaged bases, six reaction pathways were designed for monofunctional and difunctional deglycosylation of neutral bases and protonated bases. The results show that the QM/MM(ABEEM) method accurately simulates the polarization effect, charge transfer effect, activation energy and other properties of the reaction process. The process in which the active residue Asp activates the nucleophile H2O to attack the protonated base is the preferred path. The average activation energy and free activation energy of the protonated base are 7.00-14.00 kcal mol-1 lower than that of the neutral base. The study in this paper is helpful to understand the mechanism of repair enzymes in repairing bases.

Dual-wavelength off-axis digital holography in ImageJ: toward real-time phase retrieval using CUDA streams.

An ImageJ plug-in is developed to realize automatic real-time phase reconstruction for dual-wavelength digital holography (DH). This plug-in assembles the algorithms, including automatic phase reconstruction based on the division algorithm and post-processing. These algorithms are implemented and analyzed using a CPU and GPU, respectively. To hide the CPU-to-GPU data transfer latency, an optimization scheme using Compute Unified Device Architecture (CUDA) streams is proposed in ImageJ. Experimental results show that the proposed plug-in can perform faster reconstruction for dual-wavelength DH, resulting in frame rates up to 48 fps even for one-megapixel digital holograms on a normal PC. In other words, the proposed plug-in can realize real-time phase reconstruction for dual-wavelength digital holographic videos.

Phylogenomics of the Liquorilactobacillus Genus.

The genus Liquorilactobacillus is a new genus commonly found in wine and plants. Despite its significance, previous studies on Liquorilactobacillus are primarily focused on phenotypic experiments, with limited genome-level studies. This study used comparative genomics to analyze 24 genomes from the genus Liquorilactobacillus, including two novel sequenced strains (IMAU80559 and IMAU80777). A phylogenetic tree of 24 strains was constructed based on 122 core genes and divided into two clades, A and B. Significant differences in GC content were observed between the two clades (P = 10e-4). Additionally, change revealed to suggests that clade B has more exposure to prophage infection having an upgraded immune system. Further analysis of functional annotation and selective pressure suggests that clade A was subjected to greater selection pressure than B clade (P = 3.9e-6) and had higher number of functional types annotated than clade B (P = 2.7e-3), while clade B had a lower number of pseudogenes than clade A (P = 1.9e-2). The findings suggest that differently prophages and environmental stress may have influenced the common ancestor of clades A and B during evolution, leading to the development of two distinct clades.

Differential Expressions of ADAM28 and ADAMTSL3 in Gingival Tissue of Patients with Periodontitis.

The modulation of gene expression via DNA methylation modifications is relevant to the pathogenesis of periodontitis. This study aimed at identifying novel biomarkers in gingival tissues from periodontitis by integrally analyzing methylation profiles and gene expression data. Differential gene expressions (DGEs) of dataset GSE106090 were obtained from the Gene Expression Omnibus (GEO) database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. DNA methylation DGEs (DM-DGEs) were analyzed from dataset GSE173082. After integrating these two datasets, expressions of common genes were validated in gingival tissues from healthy controls and periodontitis patients by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. GO analysis of 748 upregulated and 847 downregulated DEGs from the GSE106090 dataset revealed that immune response-regulating signaling pathway, cell-cell junction and signaling receptor activator activity as the top enriched biological process (BP), cellular component (CC) and molecular function (MF), respectively. DEGs were mainly enriched in cytokine-cytokine receptor interaction, Ras signaling pathway, and chemokine signaling pathway. There was one up-regulated mRNA with hypo-methylated gene [ADAM28 (a disintegrin and metalloproteinase 28)] and one down-regulated mRNA with hyper-methylated gene [ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like-3)] after integrating GSE106090 and GSE173082 datasets. Increased ADAM28 expression was validated in gingival tissues from periodontitis patients as compared to the healthy controls with decreased ADAMTSL3 expression, which were correlated with disease stage. ADAM28 and ADAMTSL3 may act as novel biomarkers in gingival tissues from periodontitis by a comprehensive analysis of bioinformatics methods and executed validation.

Correlation of ultrasound features with Bcl-2 protein expression in basal cell carcinomas (BCCs).

BACKGROUND: The expression of the Bcl-2 protein is frequently observed in basal cell carcinomas (BCCs), making it a significant biological marker and potential therapeutic target. Skin ultrasonography offers a noninvasive means of obtaining anatomical information about cutaneous tumors. OBJECTIVES: The purpose of this study was to investigate the correlation between ultrasound features and Bcl-2 expression in BCCs, to provide a reference for developing pharmacological treatment plans. METHODS: According to the Bcl-2 protein expression, 74 BCCs confirmed by surgical pathology were divided into high Bcl-2 expression BCCs (HB-BCCs) and low Bcl-2 expression BCCs (LB-BCCs). Preoperative lesion ultrasound features were analyzed retrospectively based on Liang's criteria, which included the following features: shape, surface, keratinization, base, infiltration level, internal echogenicity, distribution of hyperechoic spots, posterior echogenic changes, internal Doppler signal, and lesion size (maximum diameter and infiltration depth). The differences of two groups were compared using a chi-square test or a paired t-test. RESULTS: Based on ultrasound features, cystic areas were more frequent in LB-BCCs (χ2 = 7.015, P = .008). Furthermore, LB-BCCs exhibited greater infiltration depth than HB-BCCs (4.86 ± 2.12 mm vs. 2.72 ± 1.40 mm, P = .000), had a higher propensity to infiltrate the subcutaneous tissue (χ2 = 12.422, P = .002), and displayed a more abundant internal Doppler signal within the lesions (χ2 = 24.696, P = .000). Conversely, maximum diameter of the lesions, shape, surface, keratinization, base, hyperechoic spots distribution, and posterior echogenic changes of the lesions did not differ significantly between the two groups. CONCLUSIONS: Ultrasound features are correlated with Bcl-2 protein expression level in BCCs. LB-BCCs show greater infiltration depth, subcutaneous infiltration, more cystic changes and more abundant internal Doppler signal than HB-BCCs, which may suggest a potential basis for drug selection in BCC chemotherapy.

Acuminatums E and F, two new cyclic lipopeptides from Fusarium lateritium HU0053 and their antifungal activity.

Two new cyclic lipopeptides, acuminatums E (1) and F (2), together with four known cyclic lipopeptides, acuminatums A-D (3-6) were isolated from the corn culture of endophytic Fusarium lateritium HU0053. Their structures were elucidated by spectroscopic and advanced Marfey's amino acid analysis. All compounds were found to exhibit antifungal activities against Penicillium digitatum. Acuminatum F (2), a new cyclic lipopeptide containing an unusual 3, 4-dihydroxy-phenylalanine unit exhibited the strongest antifungal activities with inhibition zone of 6.5 mm at the dose of 6.25 µg. Therefore, acuminatum F might be a potential environmental-friendly preservative for citrus fruits.

Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics.

Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used it to determine the drug concentrations in the plasma of rats after intravenous dosing in different genders and dosages. After pretreating the plasma samples with an acetonitrile-water-ammonia solution (70:30:1.25, v/v/v), liquid chromatographic separations were efficiently achieved with a XBridge C18 column using a 5 min gradient system of aqueous ammonium bicarbonate and 95% acetonitrile-water solution (95:5, v/v) as the eluent. The GMDTC and metolazone (internal standard, IS) detection were carried out using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS), monitored at m/z 390.06-324.1 (for the GMDTC, tR: 2.03 min) and m/z 366.0-259.2 (for IS, tR: 3.88 min). The GMDTC was stable under various testing conditions, and this analytical method conforms to the verification standard of biological analysis methods. The half-life (t1/2) was determined to be 0.54-0.65 h for the intravenous, mean distribution volume and clearances were 1.08-2.08 L/kg and 1-3 L/h/kg, respectively. The AUC0-t and AUC0-∞ found after increasing the dosage exhibited a linear relationship with the administered dose. There were no statistically significant differences in the values obtained for the different genders at dosages of 50, 100 and 250 mg/kg, respectively (p > 0.05). This is the first report of a bioanalytical method to quantify GMDTC in rat plasma using LC-MS/MS, which provides useful information for the study of its pharmacological effects and clinical applications.

[Current status, trends, and challenges of continuous manufacturing technology for oral traditional Chinese medicine solid preparations].

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.