Potential role of tanycyte-derived neurogenesis in Alzheimer's disease.

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly, metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore, the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood-brain barrier function. However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.

[Annexin A1 activates the G protein-coupled formyl peptide receptor type 2-dependent endothelial nitric oxide synthase pathway to alleviate sepsis associated acute lung injury].

OBJECTIVE: To investigate whether annexin A1 (ANXA1) improves sepsis-induced lung injury by activating G protein-coupled formyl peptide receptor type 2 (FPR2)-dependent endothelial nitric oxide synthase (eNOS) pathway. METHODS: Twenty-four male SD rats were randomly divided into normal group (Control group), lipopolysaccharide (LPS) induced lung injury model group (LPS group), LPS+ANXA1 mimetic peptide group (LPS+Ac2-26 group) and LPS+ANXA1 mimetic peptide+FPR2 inhibitor group (LPS+Ac2-26+WRW4 group), with 6 rats in each group. On the third day before modeling, rats of the LPS+Ac2-26 group were injected with 1 mg/kg Ac2-26 by the tail vein and rats of LPS+Ac2-26+WRW4 group were injected with 1 mg/kg Ac2-26 and 2.2 mg/kg WRW4 by the tail vein. The rats of control group and LPS group were injected same volume of physiological saline. After 48 hours of modeling, the rats were anesthetized and the carotid blood was taken to detect the oxygenation index (OI). Lung tissue was taken from the euthanized rats. The wet/dry (W/D) ratio was determined. The pathological changes of lung tissue were observed under light microscope and pathological score was performed. The levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1ß, IL-6, IL-10), malondialdehyde (MDA) and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). The protein expressions of eNOS, inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) were detected by Western blotting. RESULTS: Under light microscope, compared with LPS group, the infiltration degree of inflammatory cells in the lung tissue of LPS+Ac2-26 group was reduced, and the thickness of the alveolar septum was improved. The degree of inflammatory cell infiltration in the lung tissue of LPS+Ac2-26+WRW4 group was more severe than that of LPS+Ac2-26 group, and the thickness of the alveolar septum increased. These findings suggested that ANXA1 significantly inhibited inflammatory cell infiltration and improved alveolar septal thickness, WRW4 reversed the lung improvement effects of ANXA1. Compared with control group, OI in LPS group was significantly decreased, and W/D ratio, pathological score and TNF-α, IL-1ß, IL-6, MDA and MPO levels in lung tissue were significantly increased. Compared with LPS group, OI and IL-10 levels in lung tissue were significantly increased in LPS+Ac2-26 group, while W/D ratio, pathological score, TNF-α, IL-1ß, IL-6, MDA and MPO levels in lung tissue were significantly decreased. These results indicated that ANXA1 can improve the oxygenation capacity, improve lung tissue leakage, reduce edema, and inhibit lung tissue inflammation in rats with lung injury. Compared with LPS+Ac2-26 group, the LPS+Ac2-26+WRW4 group showed significant decreases in OI and lung tissue IL-10 level [OI (mmHg, 1 mmHg ≈ 0.133 kPa): 132.16±24.00 vs. 248.67±18.70, IL-10 (ng/L): 27.30±3.04 vs. 36.10±3.92, both P < 0.05], the lung tissue W/D ratio, pathological score and levels of TNF-α, IL-1ß, IL-6, MDA and MPO were significantly increased [W/D ratio: 5.29±0.02 vs. 4.83±0.02, pathological score: 5.00±0.28 vs. 2.67±0.52, TNF-α (ng/L): 39.80±4.36 vs. 32.10±2.15, IL-1ß (ng/L): 200.00±15.68 vs. 152.60±9.74, IL-6 (ng/L): 181.50±18.02 vs. 148.50±7.34, MDA (mmol/mg): 82.01±8.22 vs. 70.43±5.69, MPO (pg/mg): 6.50±0.32 vs. 4.60±0.56, all P < 0.05]. These results suggested that WRW4 could block the above improvement of ANXA1. Western blotting results showed that compared with control group, the expression of eNOS, iNOS and NF-κB in LPS group was significantly up-regulated. Compared with LPS group, the protein expression of eNOS in LPS+Ac2-26 group was significantly up-regulated (eNOS/ß-actin: 0.25±0.01 vs. 0.14±0.01, P < 0.05), and the protein expression of iNOS and NF-κB was significantly down-regulated (iNOS/ß-actin: 0.09±0.02 vs. 0.12±0.02, NF-κB/ß-actin: 0.35±0.06 vs. 0.59±0.13, both P < 0.05). These findings suggested that ANXA1 might activate the eNOS pathway and down-regulate the expression of NF-κB. Compared with LPS+Ac2-26 group, the protein expression of eNOS in LPS+Ac2-26+WRW4 group was significantly down-regulated (eNOS/ß-actin: 0.17±0.02 vs. 0.25±0.01, P < 0.05), while the protein expression of iNOS and NF-κB was significantly up-regulated (iNOS/ß-actin: 0.12±0.02 vs. 0.09±0.02, NF-κB/ß-actin: 0.52±0.10 vs. 0.35±0.06, both P < 0.05). These results suggested that WRW4 blocked the activation of the eNOS pathway by ANXA1. CONCLUSIONS: ANXA1 can improve lung injury associated with sepsis by activating FPR2-dependent eNOS pathway.

Research progress and application of chitosan dressings in hemostasis: A review.

Hemorrhage affects human health, and severe bleeding remains a leading contributor to trauma-related mortality. The speed and effectiveness of the application of hemostatic materials are critical. Conventional hemostatic dressings such as bandages and gauze are gradually being replaced by new types of hemostatic dressings due to their poor hemostatic and antibacterial properties. Chitosan, a biopolymer, is biodegradable and nontoxic and possesses hemostatic and antibacterial properties. Chitosan induces hemostasis through direct contact with red corpuscles and platelets, independent of the coagulation pathways of the host, rendering it an optimal hemostatic dressing. It is widely used in wound care, particularly to stop bleeding, promote wound healing, and provide antimicrobial properties. This article reviews the recent research and development of chitosan-based hemostatic dressings, focusing on trauma hemostasis, burn hemostasis, diabetic skin ulcer hemostasis and other aspects. It also emphasizes the significance of chitosan dressings in wound hemostasis and healing, identifies their research opportunities in hemostasis and wound healing, and explores new research directions.

The role of Keap1-Nrf2 signaling pathway in the treatment of respiratory diseases and the research progress on targeted drugs.

Lungs are exposed to external oxidants from the environment as in harmful particles and smog, causing oxidative stress in the lungs and consequently respiratory ailment. The NF-E2-related factor 2 (Nrf2) is the one with transcriptional regulatory function, while its related protein Kelch-like ECH-associated protein 1 (Keap1) inhibits Nrf2 activity. Together, they form the Keap1-Nrf2 pathway, which regulates the body's defense against oxidative stress. This pathway has been shown to maintain cellular homeostasis during oxidative stressing, inflammation, oncogenesis, and apoptosis by coordinating the expression of cytoprotective genes and making it a potential therapeutic target for respiratory diseases. This paper summarizes this point in detail in Chapter 2. In addition, this article summarizes the current drug development and clinical research progress related to the Keap1-Nrf2 signaling pathway, with a focus on the potential of Nrf2 agonists in treating respiratory diseases. Overall, the article reviews the regulatory mechanisms of the Keap1-Nrf2 signaling pathway in respiratory diseases and the progress of targeted drug research, aiming to provide new insights for treatment.

Deciphering regulatory patterns in a mouse model of hyperoxia-induced acute lung injury.

Background: Oxygen therapy plays a pivotal role in treating critically ill patients in the intensive care unit (ICU). However, excessive oxygen concentrations can precipitate hyperoxia, leading to damage in multiple organs, with a notable effect on the lungs. Hyperoxia condition may lead to hyperoxia-induced acute lung injury (HALI), deemed as a milder form of acute respiratory distress syndrome (ARDS). Given its clinical importance and practical implications, there is a compelling need to investigate the underlying pathogenesis and comprehensively understand the regulatory mechanisms implicated in the development of HALI. Results: In this study, we conducted a mouse model with HALI and performed regulatory mechanism analysis using RNA-seq on both HALI and control group. Comprehensive analysis revealed 727 genes of significant differential expression, including 248 long non-coding RNAs (lncRNAs). Also, alternative splicing events were identified from sequencing results. Notably, we observed up-regulation or abnormal alternative splicing of genes associated with immune response and ferroptosis under hyperoxia conditions. Utilizing weighted gene co-expression network analysis (WGCNA), we ascertained that genes involved in immune response formed a distinct cluster, showcasing an up-regulated pattern in hyperoxia, consistent with previous studies. Furthermore, a competing endogenous RNA (ceRNA) network was constructed, including 78 differentially expressed mRNAs and six differentially expressed lncRNAs, including H19. These findings uncover the intricate interplay of multiple transcriptional regulatory mechanisms specifically tailored to the pulmonary defense against HALI, substantiating the importance of these non-coding RNAs in this disease context. Conclusions: Our results provide new insights into the potential mechanisms and underlying pathogenesis in the development of HALI at the post-transcriptional level. The findings of this study reveal potential regulatory interactions and biological roles of specific lncRNAs and genes, such as H19 and Sox9, encompassing driven gene expression patterns, alternative splicing events, and lncRNA-miRNA-mRNA ceRNA networks. These findings may pave the way for advancing therapeutic strategies and reducing the risk associated with oxygen treatment for patients.

Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles.

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively). Both PV2 wtVLP and sVLP are efficiently produced in Pichia pastoris yeast. The PV2 sVLP displays higher levels of D-antigen and significantly enhanced thermostability than the wtVLP. Unlike the wtVLP, the sVLP elicits neutralizing antibodies in mice at levels comparable to those induced by inactivated polio vaccine. The addition of an aluminum hydroxide adjuvant to sVLP results in faster induction and a higher magnitude of neutralizing antibodies. Furthermore, our cryo-EM structural study of both sVLP and wtVLP reveals a native conformation for the sVLP and a non-native expanded conformation for the wtVLP. Our work not only validates the yeast-produced PV2 sVLP as a promising vaccine candidate with high production potential but also sheds light on the structural mechanisms that underpin the assembly and immunogenicity of the PV2 sVLP. These findings may expedite the development of sVLP-based PV vaccines.

Efficient and robust reverse genetics system for bovine rotavirus generation and its application for antiviral screening.

Unveiling the molecular mechanisms underlying rotavirus replication and pathogenesis has been hampered by the lack of a reverse genetics (RG) system in the past. Since 2017, multiple plasmid-based RG systems for simian, human, and murine-Like rotaviruses have been established. However, none of the described methods have supported the recovery of bovine rotaviruses (BRVs). Here, we established an optimized plasmid-based RG system for BRV culture-adapted strain (BRV G10P [15] BLR) and clinical isolates (BRV G6P[1] C73, G10P[11] HM26) based on a BHK-T7 cell clone stably expressing T7 polymerase. Furthermore, using this optimized RG system, we successfully rescued the reporter virus BRV rC73/Zs, rHM26/Zs and rBLR/Zs, harboring a genetically modified 1.8-kb segment 7 encoding full-length nonstructural protein 3 (NSP3) fused to ZsGreen, a 232-amino acid green fluorescent protein. Analysis of the stability of genomic insertions showed that the rC73/Zs and rBLR/Zs replicated efficiently and were genetically stable in seven rounds of serial passaging, while rHM26/Zs can be stabilized only up to the third generation, indicating that the BRV segment composition may influence the viral fitness. In addition, we adopted the recombinant reporter viruses for high-throughput screening application and discovered 12 candidates out of 1440 compounds with potential antiviral activities against rotavirus. In summary, this improved RG system of BRVs represents an important tool with great potential for understanding the molecular biology of BRV and facilitates the development of novel therapeutics and vaccines for BRV.

Erosion of cultivated kelp facilitates dissolved organic carbon release.

Growing trend of interests for contributions of cultivation of kelp to carbon sequestration have been driven globally. Saccharina japonica is an important cultivated seaweed, with erosion phenomenon usually occurs at the distal part of the frond in S. japonica throughout the growth cycle. However, the dynamics of dissolved organic carbon (DOC) release induced by erosion of S. japonica are not well understood. This study revealed that erosion induced a substantial increase in DOC release, with a 14% increase under low light (LL) conditions and a 54% increase under high light (HL) conditions. A 10 cm of long slit cut into the distal part of S. japonica increased the rate of DOC release by 56% under LL conditions, and by 13% under HL conditions. Additionally, the epibiotic microorganisms facilitate the release of DOC, and the effects were even more pronounced in erosive S. japonica. Conversely, the proximal part of S. japonica exhibited a higher photosynthetic carbon fixation capacity, with a carbon-to-nitrogen (C/N) ratio approximately 1.76 times higher than that in distal part. During the growth of S. japonica, excess photosynthetic products were often transported from the proximal part into distal part, further facilitating DOC release. In summary, DOC released induced by erosion of S. japonica could make contributions to oceanic carbon sequestration.

Sex-specific hypothalamic neuropathology and glucose metabolism in an amyloidosis transgenic mouse model of Alzheimer's disease.

BACKGROUND: Amyloid toxicity and glucose metabolic disorders are key pathological features during the progression of Alzheimer's disease (AD). While the hypothalamus plays a crucial role in regulating systemic energy balance, the distribution of amyloid plaques in the preoptic, anterior, tuberal, and mammillary regions of the hypothalamus in AD mice, particularly across both sexes, remains largely unclear. Our ongoing research aims to explore hypothalamic neuropathology and glucose metabolic disturbances in a well-described APP/PS1 mouse model of AD. RESULTS: Immunocytochemical staining revealed that Old-AD-Female mice exhibited a greater hypothalamic Amyloid ß (Aß) burden than their Old-AD-Male counterparts, with the mammillary bodies showing the most severe accumulation. Analysis of ionized calcium binding adaptor molecule 1 (IBA1) immunoreactivity and Iba1 mRNA indicated differential microgliosis based on sex, while tanycytic territory and ZO-1 tight junction protein expression remained stable in AD mice. Moreover, sex-specific peripheral glucose metabolic parameters (random and fasting blood glucose) seemed to be exacerbated by age. Old AD mice of both sexes exhibited limited hypothalamic activation (c-Fos + cells) in response to blood glucose fluctuations. Hypothalamic Glut 1 expression decreased in young but increased in old female AD mice compared with age-matched male AD mice. Pearson correlation analysis further supported a negative correlation between hypothalamic Aß load and random blood glucose in old AD groups of both genders, shedding light on the mechanisms underlying this amyloidosis mouse model. CONCLUSION: Aged APP/PS1 mice exhibit sex-specific hypothalamic neuropathology and differential glucose metabolism, highlighting distinct pathological mechanisms within each gender.

Progress in culture technology and active substance research on Nostoc sphaeroides Kützing.

Nostoc sphaeroides Kützing is a freshwater edible cyanobacterium that is rich in active substances such as polysaccharides, proteins and lipids; it has a variety of pharmacological effects such as antioxidant, anti-inflammatory, antitumor and cholesterol-lowering effects; and is often used as a traditional Chinese medicine with many potential applications in food, cosmetics, medical diagnostics and disease treatment. However, to meet the needs of different fields, such as medicine, there is an urgent need for basic research and technological innovation in culture technology, extraction and preparation of active substances, and the pharmacological mechanism of N. sphaeroides. This paper reviews the pharmacological effects of N. sphaeroides active substances, discusses current culture techniques and methods for extracting active components, and outlines the challenges encountered in cultivating and industrializing N. sphaeroides while discussing future development trends. © 2024 Society of Chemical Industry.

Characterizing and decoding the key odor compounds of Spirulina platensis at different processing stages by sensomics.

Processing is an indispensable technology in the preparation of Spirulina platensis (S. platensis). The key odorants in liquids, muds, and powders from S. platensis (NM and GZ) were characterized. A total of 90 odorants were identified and 41 odorants were sniffed with the flavor dilution (FD) factors ranging from 1 to 729. Among them, nonanal, decanal, d-limonene, ß-cyclocitral, and ß-ionone with FD factors ≥1 were detected in S. platensis during the whole processing stages. In addition, heptanal, (E, E)-2,4-nonadienal, trans-4,5-epoxy-(E)-2-decenal, 1-hepten-3-one, isophorone, 3-ethyl-2,5-dimethylpyrazine, and α-ionone exhibited higher odor activity values in powders; ß-myrcene, methional, and S-methyl methanethiosulphonate were key odorants in muds; while trans-3-penten-2-ol was key odorant in liquids. Besides, the GZ-mud presented stronger earthy and fishy odor than NM-mud. S. platensis powders have the stronger grassy odor, roasted odor, and marine odor than S. platensis muds. Overall, drying process promotes the formation of aldehydes, heterocyclic compounds, and terpenoids.

Fractional-Order Boosted Hybrid Young's Double-Slit Experimental Optimizer for Truss Topology Engineering Optimization.

Inspired by classical experiments that uncovered the inherent properties of light waves, Young's Double-Slit Experiment (YDSE) optimization algorithm represents a physics-driven meta-heuristic method. Its unique search mechanism and scalability have attracted much attention. However, when facing complex or high-dimensional problems, the YDSE optimizer, although striking a good balance between global and local searches, does not converge as fast as it should and is prone to fall into local optimums, thus limiting its application scope. A fractional-order boosted hybrid YDSE, called FYDSE, is proposed in this article. FYDSE employs a multi-strategy mechanism to jointly address the YDSE problems and enhance its ability to solve complex problems. First, a fractional-order strategy is introduced into the dark edge position update of FYDSE to ensure more efficient use of the search potential of a single neighborhood space while reducing the possibility of trapping in a local best. Second, piecewise chaotic mapping is constructed at the initial stage of the population to obtain better-distributed initial solutions and increase the convergence rate to the optimal position. Moreover, the low exploration space is extended by using a dynamic opposition strategy, which improves the probability of acquisition of a globally optimal solution. Finally, by introducing the vertical operator, FYDSE can better balance global exploration and local exploitation and explore new unknown areas. The numerical results show that FYDSE outperforms YDSE in 11 (91.6%) of cec2022 sets. In addition, FYDSE performs best in 8 (66.6%) among all algorithms. Compared with the 11 methods, FYDSE obtains the optimal best and average weights for the 20-bar, 24-bar, and 72-bar truss problems, which proves its efficient optimization capability for difficult optimization cases.

A Multi-Strategy Improvement Secretary Bird Optimization Algorithm for Engineering Optimization Problems.

Based on a meta-heuristic secretary bird optimization algorithm (SBOA), this paper develops a multi-strategy improvement secretary bird optimization algorithm (MISBOA) to further enhance the solving accuracy and convergence speed for engineering optimization problems. Firstly, a feedback regulation mechanism based on incremental PID control is used to update the whole population according to the output value. Then, in the hunting stage, a golden sinusoidal guidance strategy is employed to enhance the success rate of capture. Meanwhile, to keep the population diverse, a cooperative camouflage strategy and an update strategy based on cosine similarity are introduced into the escaping stage. Analyzing the results in solving the CEC2022 test suite, the MISBOA both get the best comprehensive performance when the dimensions are set as 10 and 20. Especially when the dimension is increased, the advantage of MISBOA is further expanded, which ranks first on 10 test functions, accounting for 83.33% of the total. It illustrates the introduction of improvement strategies that effectively enhance the searching accuracy and stability of MISBOA for various problems. For five real-world optimization problems, the MISBOA also has the best performance on the fitness values, indicating a stronger searching ability with higher accuracy and stability. Finally, when it is used to solve the shape optimization problem of the combined quartic generalized Ball interpolation (CQGBI) curve, the shape can be designed to be smoother according to the obtained parameters based on MISBOA to improve power generation efficiency.

Habitat for Coilia nasus in southern Zhejiang Province, China, based on a maximum entropy model.

As an important fishery resource and endangered species, studying the habitat of Coilia nasus (C. nasus) is highly significant. This study used fishery survey data from southern Zhejiang coastal waters from 2016 to 2020, employing a maximum entropy model (MaxEnt) to map the habitat distribution of C. nasus. Model performance was evaluated using two metrics: the area under the curve (AUC) of the receiver operating characteristic curve for the training and test sets and true skill statistics (TSS). This study aimed to predict the habitat distribution of C. nasus and explore how environmental variables influence habitat suitability. The results indicated that the models for each season had strong predictive performance, with AUC values above 0.8 and TSS values exceeding 0.6, indicating that they could accurately predict the presence of C. nasus. In the study area, C. nasus was primarily found in brackish or marine waters near bays and coastal islands. Among all environmental factors, salinity (S) and bottom temperature (BOT) had the highest correlations with habitat distribution, although these correlations varied across seasons. The findings of this study provide empirical evidence and a reference for the conservation and management of C. nasus and for the designation of its protected areas.

Wedelolactone inhibits ferroptosis and alleviates hyperoxia-induced acute lung injury via the Nrf2/HO-1 signaling pathway.

Hyperoxia-induced acute lung injury (HALI) is a complication of oxygen therapy. Ferroptosis is a vital factor in HALI. This paper was anticipated to investigate the underlying mechanism of Wedelolactone (WED) on ferroptosis in HALI. The current study used hyperoxia to injure two models, one HALI mouse model and one MLE-12 cell injury model. We found that WED treatment attenuated HALI by decreasing the lung injury score and lung wet/dry weight ratio and alleviating pathomorphological changes. Then, the inflammatory reaction and apoptosis in HALI mice and hyperoxia-mediated MLE-12 cells were inhibited by WED treatment. Moreover, WED alleviated ferroptosis with less iron accumulation and reversed expression alterations of ferroptosis markers, including MDA, GSH, GPX4, SLC7A11, FTH1, and TFR1 in hyperoxia-induced MLE-12 cells in vitro and in vivo. Nrf2-KO mice and Nrf2 inhibitor (ML385) decreased WED's ability to protect against apoptosis, inflammatory response, and ferroptosis in hyperoxia-induced MLE-12 cells. Collectively, our data highlighted the alleviatory role of WED in HALI by activating the Nrf2/HO-1 pathway.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

High-yield magnetosome production of Magnetospirillum magneticum strain AMB-1 in flask fermentation through simplified processing and optimized iron supplementation.

OBJECTIVES: Developing a simplified flask fermentation strategy utilizing magnetotactic bacterium AMB-1 and optimized iron supplementation for high-yield magnetosome production to address the challenges associated with magnetosome acquisition. RESULTS: A reliable processing for the pure culture of AMB-1 was established using standard laboratory consumables and equipment. Subsequently, the medium and iron supplementation were optimized to enhance the yield of AMB-1 magnetosomes. The mSLM supported higher biomass accumulation in flask fermentation, reaching an OD565 of ~ 0.7. The premixed solution of ferric quinate and EDTA-Fe (at a ratio of 0.5:0.5 and a concentration of 0.4 mmol/L) stabilized Fe3+ and significantly increased the reductase activity of AMB-1. Flask fermentations with an initial volume of 15 L were then conducted employing the optimized fermentation strategy. After two rounds of iron and nutrient supplementation, the magnetosome yield reached 185.7 ± 9.5 mg/batch (approximately 12 mg/L), representing the highest AMB-1 flask fermentation yield to our knowledge. CONCLUSION: A flask fermentation strategy for high-yield magnetsome production was developed, eliminating the need for bioreactors and greatly simplifying the process of magnetosome acquisition.

Asymmetric Total Synthesis of Euphordraculoate A and Pedrolide.

Here we report the asymmetric total syntheses of two rearranged tigliane diterpenoids, euphordraculoate A and pedrolide. A reductive dihydroxylation cascade and Nazarov cyclization were performed to generate euphordraculoate A, which was subjected to a cascade of Eu-promoted dienyl enolization, intramolecular Diels-Alder reaction and enol-ketone tautomerization to afford pedrolide, a pathway consistent with our proposal for the biogenesis of pedrolide.

Phylogenetic distribution and characterization of conserved C-di-GMP metabolizing proteins in filamentous cyanobacterium Arthrospira.

Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger in bacteria that regulates multiple biological functions, including biofilm formation, virulence, and intercellular communication. However, c-di-GMP signaling is virtually unknown in economically important filamentous cyanobacteria, Arthrospira. In this study, we predicted 31 genes encoding GGDEF-domain proteins from A. platensis NIES39 as potential diguanylate cyclases (DGCs). Phylogenetic distribution analysis showed five genes (RS09460, RS04865, RS26155, M01840, and E02220) with highly conserved distribution across 25 Arthrospira strains. Adc1 encoded by RS09460 was further characterized as a typical DGC. By establishing the genetic transformation system of Arthrospira, we demonstrated that the overexpression of Adc1 promoted the production of extracellular polymeric substances (EPS), which in turn caused the aggregation of filaments. We also confirmed that RS04865 and RS26155 may encode active DGCs, while enzymatic activity assays showed that proteins encoded by M01840 and E02220 have phosphodiesterase (PDE) activity. Meta-analysis revealed that the expression profiles of RS09460 and RS04865 were unaffected under 31 conditions, suggesting that they may function as conserved genes in maintaining the basal level of c-di-GMP in Arthrospira. In summary, this report will provide the basis for further studies of c-di-GMP signal in Arthrospira.

Soil conditioner improves soil properties, regulates microbial communities, and increases yield and quality of Uncaria rhynchophylla.

Uncaria rhynchophylla is an important traditional herbal medicine in China, and the yield and quality of Uncaria rhynchophylla can be improved by suitable soil conditioners because of changing the soil properties. In this paper, Uncaria rhynchophylla associated alkaloids and soil microbial  communities were investigated. The field experiment was set up with the following control group: (M1, no soil conditioner) and different soil conditioner treatment groups (M2, biomass ash; M3, water retention agent; M4, biochar; M5, lime powder and M6, malic acid). The results showed that M2 significantly increased the fresh and dry weight and the contents of isorhynchophylline, corynoxeine, isocorynoxeine, and total alkaloids. Acidobacteria, Proteobacteria, Actinobacteria, and Chloroflexi were major bacterial phyla. Correlation analysis showed that fresh and dry weight was significantly positively correlated with Acidobacteria, while alkali-hydrolyzable nitrogen, phosphatase activity, fresh and dry weight, corynoxeine, and isocorynoxeine were significantly negatively correlated with Chloroflexi. The application of soil conditioner M2 increased the abundance of Acidobacteria and decreased the abundance of Chloroflexi, which contributed to improving the soil nutrient content, yield, and quality of Uncaria rhynchophylla. In summary, biomass ash may be a better choice of soil conditioner in Uncaria rhynchophylla growing areas.