Research on the Application of Molecular Image Processing in Rice Quality Inspection.

Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.

Plant-derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety.

Rice-fish coculture without phosphorus addition improves paddy soil nitrogen availability by shaping ammonia-oxidizing archaea and bacteria in subtropical regions of South China.

Rice-fish coculture (RFC), as a traditional agricultural strategy in China, can optimally utilize the scarce resource, especially in subtropical regions where phosphorus (P) deficiency limits agricultural production. However, ammonia-oxidizing archaea (AOA) and bacteria (AOB) are involved in the ammonia oxidation, but it remains uncertain whether their community compositions are related to the RFC combined with and without P addition that improves soil nitrogen (N) use efficiency. Here, a microcosm experiment was conducted to assess the impacts of RFC combined with and without inorganic P (0 and 50 mg P kg-1 as KH2PO4) addition on AOA and AOB community diversities, enzyme activities and N availability. The results showed that RFC significantly increased available N content without P addition compared with P addition. Moreover, RFC significantly increased urease activity and AOA shannon diversity, and reduced NAG activity and AOB shannon diversity without P addition, respectively. Higher diversity of AOA compared with that of AOB causes greater competition for resources and energy within their habitats, thereby resulting in lower network complexity. Our findings indicated that the abundances of AOA and AOB are influenced through the introduction of fish and/or P availability, of which AOB is linked to N availability. Overall, RFC could improve paddy soil N availability without P addition in subtropical region, which provides a scientific reference for promoting the practices that reduce N fertilizer application in RFC.

Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method.

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.

Different responses of marine microalgae Phaeodactylum tricornutum upon exposures to WAF and CEWAF of crude oil: A case study coupled with stable isotopic signatures.

Increasing use of chemical dispersants for oil spills highlights the need to understand their adverse effects on marine microalgae and nutrient assimilation because the toxic components of crude oil can be more bioavailable. We employed the crude oil water-accommodated fraction (WAF) and chemically enhanced WAF (CEWAF) to compare different responses in marine microalgae (Phaeodactylum tricornutum) coupled with stable isotopic signatures. The concentration and proportion of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs), which are key toxic components in crude oil, increased after dispersant addition. CEWAF exposure caused higher percent growth inhibition and a lower chlorophyll-a level of microalgae than those after WAF exposure. Compared with WAF exposure, CEWAF led to an enhancement in the self-defense mechanism of P. tricornutum, accompanied by an increased content of extracellular polymeric substances. 13C-depletion and carbon assimilation were altered in P. tricornutum, suggesting more HMW PAHs could be utilized as carbon sources by microalgae under CEWAF. CEWAF had no significant effects on the isotopic fractionation or assimilation of nitrogen in P. tricornutum. Our study unveiled the impact on the growth, physiological response, and nutrient assimilation of microalgae upon WAF and CEWAF exposures. Our data provide new insights into the ecological effects of dispersant applications for coastal oil spills.

Vitamin D levels and the risk of overactive bladder: a systematic review and meta-analysis.

CONTEXT: Overactive bladder is treated mainly with behavioral and drug therapy, and symptoms of urinary frequency and incontinence are challenging to eliminate. There is thus a continuous unmet need for new drugs with a substitution effect mechanism. OBJECTIVE: It not known whether vitamin D deficiency can lead to overactive bladder or urinary incontinence or whether vitamin D supplementation alleviates bladder symptoms. This comprehensive systematic review with meta-analysis was conducted to determine whether overactive bladder is associated with vitamin D deficiency. DATA SOURCES: The PubMed and Cochrane Library databases were searched systematically up to July 3, 2022. DATA EXTRACTION: Initially, 706 articles were identified in the literature search, of which 13 were included in the systematic review: 4 randomized controlled trials, 3 cohort studies, 3 cross-sectional studies, and 3 case-control studies. DATA ANALYSIS: An increased risk of overactive bladder and urinary incontinence was observed with vitamin D deficiency (odds ratio [OR] = 4.46; 95%CI, 1.03-19.33; P = 0.046 and OR = 1.30; 95%CI, 1.01-1.66; P = 0.036, respectively). Vitamin D levels were relatively low in patients with overactive bladder or urinary incontinence (SMD = -0.33; 95%CI, -0.61 to -0.06, P = 0.019). On the basis of existing data, the risk of urinary incontinence was reduced by 66% after vitamin D supplementation (OR = 0.34; 95%CI, 0.18-0.66; P = 0.001). Egger test was conducted to assess publication bias, and the results were tested for robustness using a sensitivity analysis. CONCLUSIONS: Vitamin D deficiency increases the risk of overactive bladder and urinary incontinence, and vitamin D supplementation reduces the risk of urinary incontinence. The development of new strategies to prevent or alleviate bladder symptoms is crucial. Vitamin D supplementation may be gaining recognition as an effective strategy for prevention or alleviation of bladder symptoms such as overactive bladder and incontinence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022351443.

Associations of unintended pregnancy with autism spectrum disorders and the modification of folic acid supplements.

There is limited evidence on the associations of unintended pregnancy with autism spectrum disorders (ASD). This study aimed to examine this relationship and the modification of pre-conceptional and prenatal folic acid supplements. Six thousand and five toddlers aged 16 to 30 months from seven cities of six provinces in China were eligible for participation. Information on unintended pregnancy and folic acid supplements was obtained via questionnaires from caregivers of toddlers. The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Chinese version of the Childhood Autism Rating Scale (CARS). Of the 6005 toddlers in the study (3337 boys and 2668 girls), 71 (1.18%) received the diagnosis of ASD. Generalized linear models with a logit link function showed unintended pregnancy was positively associated with ASD (odds ratios [OR] = 1.69, 95% confidence interval [CI], 1.05-2.79). Stratified estimates indicated that the association remained stable among toddlers of mothers without pre-conceptional and prenatal folic acid supplements (OR = 2.75, 95% CI, 1.04-7.27; n = 1243, 20.70%). Unintended pregnancy was associated with higher odds of ASD in 16-30 months of toddlers, and the association was consistent among toddlers of mothers without prenatal folic acid supplements. Our findings emphasize the need to raise awareness of the risk of unintended pregnancy and the benefits of folic acid supplements among Chinese women.

Organic phosphorus levels change the hyphosphere phoD-harboring bacterial community of Funneliformis mosseae.

The phoD-harboring bacterial community is responsible for organic phosphorus (P) mineralization in soil and is important for understanding the interactions between arbuscular mycorrhizal (AM) fungi and phosphate-solubilizing bacteria (PSB) at the community level for organic P turnover. However, current understanding of the phoD-harboring bacterial community associated with AM fungal hyphae responses to organic P levels remains incomplete. Here, two-compartment microcosms were used to explore the response of the phoD-harboring bacterial community in the hyphosphere to organic P levels by high-throughput sequencing. Extraradical hyphae of Funneliformis mosseae enriched the phoD-harboring bacterial community and organic P levels significantly altered the composition of the phoD-harboring bacterial community in the Funneliformis mosseae hyphosphere. The relative abundance of dominant families Pseudomonadaceae and Burkholderiaceae was significantly different among organic P treatments and were positively correlated with alkaline phosphatase activity and available P concentration in the hyphosphere. Furthermore, phytin addition significantly decreased the abundance of the phoD gene, and the latter was significantly and negatively correlated with available P concentration. These findings not only improve the understanding of how organic P influences the phoD-harboring bacterial community but also provide a new insight into AM fungus-PSB interactions at the community level to drive organic P turnover in soil.

Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect.

BACKGROUND: Gemcitabine is a first-line chemotherapeutic agent for pancreatic cancer (PC); however, most patients who receive adjuvant gemcitabine rapidly develop resistance and recurrence. Cancer-associated fibroblasts (CAFs) are a crucial component of the tumor stroma that contribute to gemcitabine-resistance. There is thus an urgent need to find a novel therapeutic strategy to improve the efficacy of gemcitabine in PC cells under CAF-stimulation. PURPOSE: To investigate if shikonin potentiates the therapeutic effects of gemcitabine in PC cells with CAF-induced drug resistance. METHODS: PC cell-stimulated fibroblasts or primary CAFs derived from PC tissue were co-cultured with PC cells to evaluate the ability of shikonin to improve the chemotherapeutic effects of gemcitabine in vitro and in vivo. Glucose uptake assay, ATP content analysis, lactate measurement, real-time PCR, immunofluorescence staining, western blot, and plasmid transfection were used to investigate the underlying mechanism. RESULTS: CAFs were innately resistant to gemcitabine, but shikonin suppressed the PC cell-induced transactivation and proliferation of CAFs, reversed CAF-induced resistance, and restored the therapeutic efficacy of gemcitabine in the co-culture system. In addition, CAFs underwent a reverse Warburg effect when co-cultured with PC cells, represented by enhanced aerobic glycolytic metabolism, while shikonin reduced aerobic glycolysis in CAFs by reducing their glucose uptake, ATP concentration, lactate production and secretion, and glycolytic protein expression. Regarding the mechanism underlying these sensitizing effects, shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects. Furthermore, shikonin promoted the effects of gemcitabine in reducing the growth of tumors derived from PC cells and CAF co-inoculation in BALB/C mice, with no significant systemic toxicity. CONCLUSION: These results indicate that shikonin reduced MCT4 expression and activation, resulting in inhibition of aerobic glycolysis in CAFs and overcoming CAF-induced gemcitabine resistance in PC. Shikonin is a promising chemosensitizing phytochemical agent when used in combination with gemcitabine for PC treatment. The results suggest that disrupting the metabolic coupling between cancer cells and stromal cells might provide an attractive strategy for improving gemcitabine efficacy.

An updated review of the genus Rhododendron since 2010: Traditional uses, phytochemistry, and pharmacology.

Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development.

Efficacy and Safety of High-Dose Vitamin D Supplementation vs Solifenacin or Standard Urotherapy for Overactive Bladder Dry in Children: A Randomized Clinical Trial.

PURPOSE: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. MATERIALS AND METHODS: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n=303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS + SU group; n=100), solifenacin (5-10 mg/d) plus SU (SOL + SU group; n=102), or SU alone (SU group; n=101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. RESULTS: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS + SU group showed greater improvements in voids/d than the SOL + SU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDS + SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOL + SU and SU groups. The VDS + SU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. CONCLUSIONS: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

[Screening and expression analysis of transcription factors involved in genuineness of Codonopsis pilosula in Shanxi].

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.

Minimally Invasive Hypoglossal Nerve Stimulator Enabled by ECG Sensor and WPT to Manage Obstructive Sleep Apnea.

A hypoglossal nerve stimulator (HGNS) is an invasive device that is used to treat obstructive sleep apnea (OSA) through electrical stimulation. The conventional implantable HGNS device consists of a stimuli generator, a breathing sensor, and electrodes connected to the hypoglossal nerve via leads. However, this implant is bulky and causes significant trauma. In this paper, we propose a minimally invasive HGNS based on an electrocardiogram (ECG) sensor and wireless power transfer (WPT), consisting of a wearable breathing monitor and an implantable stimulator. The breathing external monitor utilizes an ECG sensor to identify abnormal breathing patterns associated with OSA with 88.68% accuracy, achieved through the utilization of a convolutional neural network (CNN) algorithm. With a skin thickness of 5 mm and a receiving coil diameter of 9 mm, the power conversion efficiency was measured as 31.8%. The implantable device, on the other hand, is composed of a front-end CMOS power management module (PMM), a binary-phase-shift-keying (BPSK)-based data demodulator, and a bipolar biphasic current stimuli generator. The PMM, with a silicon area of 0.06 mm2 (excluding PADs), demonstrated a power conversion efficiency of 77.5% when operating at a receiving frequency of 2 MHz. Furthermore, it offers three-voltage options (1.2 V, 1.8 V, and 3.1 V). Within the data receiver component, a low-power BPSK demodulator was ingeniously incorporated, consuming only 42 µW when supplied with a voltage of 0.7 V. The performance was achieved through the implementation of the self-biased phase-locked-loop (PLL) technique. The stimuli generator delivers biphasic constant currents, providing a 5 bit programmable range spanning from 0 to 2.4 mA. The functionality of the proposed ECG- and WPT-based HGNS was validated, representing a highly promising solution for the effective management of OSA, all while minimizing the trauma and space requirements.

The molybdenum cofactor biosynthesis gene, OsCNX1, is essential for seedling development and seed germination in rice.

Pre-harvest sprouting (PHS) frequently occurs in rice due to the long spells of rainy weather, and causes severe yield loss and grain quality decrease. Here, we identified one PHS-related gene OsCNX1 cloned from rice PHS mutant, which encoded a molybdenum cofactor (MoCo) biosynthesis enzyme. Genetic complementation indicated OsCNX1 could rescue the PHS and seedling lethal phenotype of the mutant. Expression pattern showed that OsCNX1 was expressed in rice tissue including seedling shoot, culm, blade, and sheath of flag leaf, young panicle, and the seeds at different development stages. Overexpression of OsCNX1 significantly decreased the plant height, and the seed germination of the dormant seeds harvested from fresh panicles, comparing to the wild type (WT). In addition, 1492 differentially expressed genes (DEGs) were identified between OsCNX1-overexpressed line and WT by RNA-sequencing, which were mainly classified in plant-pathogen interaction, plant hormone signal transduction, and starch/sucrose metabolism. These results showed that OsCNX1 was not only necessary for rice seed germination, but also participated in plant development, indicating that OsCNX1 may be useful in rice breeding of PHS resistance and plant height. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-023-01424-x.

Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium Tuberculosis clearance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the 'iron-tropic' Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings.

Predictive factors and clinical efficacy of Chinese medicine Shengji ointment in the treatment of diabetic foot ulcers in the elderly: a prospective study.

Objective: This study aims to investigate the predictive factors and efficacy of traditional Chinese medicine Shengji Ointment in the treatment of diabetic foot ulcers in the elderly population, with the intent of formulating an effective predictive model for deep diabetic foot ulcer healing. The importance of this research lies in its provision of new perspectives and tools for addressing the severe health impact of diabetic foot ulcers in the elderly population, considering the complexity and diversity of its treatment methods. Methods: The study includes 180 elderly patients with Wagner grade 3-4 diabetic foot ulcers that involve the tendon or fascia. The dependent variable is the initiation time of granulation tissue development. Independent variables encompass demographic information, a treatment strategy including Shengji Ointment, pre-treatment trauma assessment data, routine blood count, and biochemical index test results. Lasso regression is employed for variable selection, and Cox regression is utilized for the construction of a prediction model. A nomogram is generated to authenticate the model. Results: The Chinese Medicine treatment approach, ulcer location, creatinine levels, BMI, and haemoglobin levels are identified as independent predictors of granulation tissue development in diabetic foot ulcers. The combined treatment of Chinese herbal Shengji ointment and bromelain positively influenced granulation tissue development. The location of plantar ulcers, impaired renal functionality, obesity, and anaemia are established as independent risk factors that might influence the speed and probability of ulcer healing. The area under the time-dependent ROC curve fluctuates between 0.7 and 0.8, demonstrating substantial discrimination and calibration of the model. Conclusion: The study ascertains that a combined treatment strategy incorporating Shengji Ointment demonstrates greater effectiveness than the use of cleansing gel debridement alone in facilitating the healing of Wagner grade 3 or higher diabetic foot ulcers. Furthermore, the predictive model developed in this research serves as a valuable tool in evaluating the efficacy of Chinese Medicine treatments like Shengji Ointment for diabetic foot ulcers in the elderly. It aids clinicians in effectively assessing and adjusting treatment strategies, thereby proving its significant application value in clinical practice. Clinical Trial Registration: (https://www.chictr.org.cn/hvshowproject.html?id=73862&v=1.5&u_atoken=b403af53-d3b9-41ae-a7e2-db5498609b0c&u_asession=01tNh69p235bMUO4CmHIXcv8Hxirl5-557Duue9QB5lGfl3mf8IvPlcs2kN2zC30voX0KNBwm7Lovlpxjd_P_q4JsKWYrT3W_NKPr8w6oU7K_AyPrQhedMUWBMR2-ZDL_KO0uwDPR9XlF566xraDvT9mBkFo3NEHBv0PZUm6pbxQU&u_asig=05Kd_Q8fjv-24MVbZpOS9ef3xuCCN-tSVH5eUoJKgNLM7E0-n0zMpW6xLq9gh9aUhkKEEA15rdDoCydncF99APBwVSaTPgEG_V_B1iT4wimdCTxV_4ZVbTlDewxyQtE4YgU4-Oza7KPi94RJ64Utel0yZfqg3Tlm-bVxFNOY-zXFP9JS7q8ZD7Xtz2Ly-b0kmuyAKRFSVJkkdwVUnyHAIJzSYJ6SfhFl0WMTCCasZ7zV2I2qfyrp5m-SELPVeREKgX_6yRmLu26qT8kGfcS-Yaeu3h9VXwMyh6PgyDIVSG1W-7D_Sko5YQtpDbs3uvezYkZcUUY4o9-zDPaoYelmMDs8u7I4TPvtCXaPp44YUJcQ9bHr-_RmKA5V8nji3daArhmWspDxyAEEo4kbsryBKb9Q&u_aref=NNH1nHSUCE6pNvCilV%2F1MD0aERs%3D), identifier (ChiCTR2000039327).

Lignans as multi-targeted natural products in neurodegenerative diseases and depression: Recent perspectives.

As the global population ages, the treatment of neurodegenerative diseases is becoming more and more important. There is an urgent need to discover novel drugs that are effective in treating neurological diseases. In recent years, natural products and their biological activities have gained widespread attention. Lignans are a class of metabolites extensively present in Chinese herbal medicine and possess good pharmacological effects. Latest studies have demonstrated their neuroprotective pharmacological activity in preventing acute/chronic neurodegenerative diseases and depression. In this review, the pharmacological effects of these disorders, the pharmacokinetics, safety, and clinical trials of lignans were summarized according to the scientific literature. These results proved that lignans mainly exert antioxidant and anti-inflammatory activities. Anti-apoptosis, regulation of nervous system functions, and modulation of synaptic signals are also potential effects. Despite the substantial evidence of the neuroprotective potential of lignans, it is not sufficient to support their use in the clinical management. Our study suggests that lignans can be used as prospective agents for the treatment of neurodegenerative diseases and depression, with a view to informing their further development and utilization.

Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and Aß generation.

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.