Quantitative analysis of soil potassium by near-infrared (NIR) spectroscopy combined with a three-step progressive hybrid variable selection strategy.

Soil potassium is a crucial nutrient element necessary for crop growth, and its efficient measurement has become essential for developing rational fertilization plans and optimizing crop growth benefits. At present, data mining technology based on near-infrared (NIR) spectroscopy analysis has proven to be a powerful tool for real-time monitoring of soil potassium content. However, as technology and instruments improve, the curse of the dimensionality problem also increases accordingly. Therefore, it is urgent to develop efficient variable selection methods suitable for NIR spectroscopy analysis techniques. In this study, we proposed a three-step progressive hybrid variable selection strategy, which fully leveraged the respective strengths of several high-performance variable selection methods. By sequentially equipping synergy interval partial least squares (SiPLS), the random forest variable importance measurement (RF(VIM)), and the improved mean impact value algorithm (IMIV) into a fusion framework, a soil important potassium variable selection method was proposed, termed as SiPLS-RF(VIM)-IMIV. Finally, the optimized variables were fitted into a partial least squares (PLS) model. Experimental results demonstrated that the PLS model embedded with the hybrid strategy effectively improved the prediction performance while reducing the model complexity. The RMSET and RT on the test set were 0.01181% and 0.88246, respectively, better than the RMSET and RT of the full spectrum PLS, SiPLS, and SiPLS-RF(VIM) methods. This study demonstrated that the hybrid strategy established based on the combination of NIR spectroscopy data and the SiPLS-RF(VIM)-IMIV method could quantitatively analyze soil potassium content levels and potentially solve other issues of data-driven soil dynamic monitoring.

Bimetallic NiCo@C with a Hollow Sea Urchin Structure Enables Li-S Batteries to Hasten the Reaction Kinetics and Effectively Inhibit the Shuttling of Polysulfides.

The "shuttle effect" and several issues related to it are seen as "obstacles" to the study and development of lithium-sulfur batteries (LSBs). This work aims at finding how to fully expose bimetallic sites and quicken the battery reaction kinetics. Here, a bimetallic NiCo-MOF and its derivative NiCo@C with a hollow sea urchin structure are produced. The obtained NiCo@C possesses a micromesoporous structure and fully disclosed bimetallic active sites because of its distinctive structure. The experimental findings demonstrate that fully exposed bimetallic active sites take on chemical adsorbents and collaborate with micromesopores as physical constraints to effectively suppress the "shuttle effect". Furthermore, the hollow sea urchin structure of NiCo@C enables a highly conductive grid, which provides channels to facilitate the movement of solvated Li+. Thanks to these advantages, the NiCo@C-based sulfur cathode offers a high initial discharge specific capacity of 924.41 mAh g-1 at 0.1 C and sustains 390.35 mAh g-1 discharge specific capacity after 100 cycles. The quick transfer of solvated lithium ions (DLi+ = 1.81 × 10-8 cm2 s-1) enables the battery to still contribute a discharge specific capacity of 367.54 mAh g-1 at 1 C. This work provides a new understanding for the structural design of positive electrodes in LSBs.

Assessing the causal relationship between plasma proteins and osteoporosis: novel insights into pathological mechanisms and therapeutic implications.

Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. PURPOSE: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. METHODS: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. RESULTS: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. CONCLUSIONS: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.

An updated review of the genus Toxorhina Loew, 1850 (Diptera, Limoniidae) from Yunnan, China with a description of a new species.

Seven species of the genus Toxorhina Loew, 1850 have been recorded from China, of which three are known to occur in Yunnan Province. Herein, all known species from Yunnan, China are reviewed with more detailed descriptions and illustrations of the male hypopygium. A species of Toxorhina belonging to the subgenus Ceratocheilus Wesché, 1910 from Yunnan, T. (C.) pianmicasp. nov., is described and illustrated as new to science.

Causality between six psychiatric disorders and digestive tract cancers risk: a two-sample Mendelian randomization study.

Associations between psychiatric disorders and digestive tract cancers have been proposed. However, the causal link between these factors remains unclear. This study pioneers Mendelian randomization (MR) analysis to explore the genetic link between psychiatric disorders and digestive tract cancers risk. We analysed data on six psychiatric disorders [schizophrenia, bipolar disorder, major depressive disorder (MDD), attention deficit hyperactivity disorder, autism spectrum disorder, and panic disorder (PD)] and digestive tract cancers [esophagus cancer (EC), gastric cancer (GC), and colorectal cancer (CRC)] from genome-wide association studies databases. Using instrumental variables identified from significant single nucleotide polymorphism associations, we employed the inverse variance weighted (IVW) method alongside the weighted median (WM) method and MR-Egger regression. The results revealed no causal link between psychiatric disorders and the risk of EC or GC. Psychiatric disorders were not identified as risk factors for CRC. Notably, PD demonstrated a lower CRC risk (OR = 0.79, 95% CI 0.66-0.93, P = 0.01). This MR analysis underscores the lack of a causal association between psychiatric disorders and digestive tract cancers risk while suggesting a potential protective effect of PD against CRC.

[A controlled clinical study of vertebroplasty for the treatment of osteoporotic vertebral compression fractures after self-made spinal positioner and manual reduction].

OBJECTIVE: To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures (OVCFs). METHODS: Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group (treatment group) and traditional Kirchner positioning group (control group). There were 30 patients in treatment group, including 4 males and 26 females, aged from 61 to 87 years old with an average of (73.61±7.17) years old;body mass index (BMI) ranged from 15.24 to 28.89 kg·m-2 with an average of (23.90±3.20) kg·m-2;bone mineral density T value ranged from -4.90 to -2.50 SD with an avergae of (-3.43±0.75) SD;fracture to operation time was 6.50 (4.00, 10.25) d;10 patients were gradeⅠ, 13 patients were gradeⅡ, and 7 patients were grade Ⅲ according to Genant classification of fracture compression. There were 31 patients in control group, including 7 males and 24 females, aged from 61 to 89 years old with an average of (73.63±8.77) years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of (23.67±2.35) kg·m-2;bone mineral density T value ranged from -4.60 to -2.50 SD with an avergae of (-3.30±0.68) SD;fracture to operation time was 6.00 (3.00, 8.00) d;11 patients were gradeⅠ, 9 patients were gradeⅡ, and 11 patients were grade Ⅲ according to Genant classification of fracture compression. The puncture times, X-ray fluoroscopy times and puncture time between two groups were observed and compared. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and timed up and go test (TUGT) were observed and compared before operation, 3 d and 1 month after operation. RESULTS: All patients were followed up for 1 to 3 months with an average of (2.10±0.80) months. Puncture times, X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00, 6.00) times, (29.53±5.89) times and 14.83(12.42, 21.20) min, respectively, while those in control group were 7.00(6.00, 8.00) times, (34.58±5.33) times, 22.19(17.33, 27.01) min, treatment group was better than those of control group (P<0.05). There were no significant differences in preoperative VAS, JOA and TUGT between two groups(P>0.05). VAS, JOA and TUGT in both groups were significantly improved after opeation(P<0.05). On the third day after operation, JOA score of treatment group was 23.00 (20.75, 25.00), which was higher than that of control group 20.00(19.00, 23.00)(P<0.05). TUGT of treatment group was 6.26(5.86, 6.57) s, which was better than that of control group 6.90(6.80, 7.14) s (P<0.05). Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group. CONCLUSION: The optimal scheme of self-made spinal locators for locating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times, shorten puncture times and reduce number of X-ray fluoroscopy times, and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walking ability of postoperative patients.

Ball-milled MoS2 with graphene shows enhanced catalytic activity for hydrogen evolution reaction.

The hydrogen evolution reaction (HER) is an important phenomenon in water splitting. Consequently, the development of an active, earth-abundant, and inexpensive HER catalyst is highly desired. MoS2 has drawn considerable interest as an HER catalyst because it is composed of non-precious metal and exhibits high catalytic activity in the nanosheet form. In this study, size-controlled MoS2 particles were synthesized by ball milling. The as-prepared samples exhibited significantly enhanced electrochemical and catalytic properties compared to those of pristine bulk MoS2. Furthermore, the HER activity improved further upon the introduction of graphene into the as-prepared ball-milled samples. In particular, the MoS2 sample ball-milled for 12 h mixed with graphene exhibited optimal performance, showing an overpotential (160 mV at 10 mA cm-2) that was ~ 335 mV lower than that of pristine bulk MoS2. The superior catalytic activity was ascribed to the exposed edge sites, sulfur vacancies, and 1T phase of MoS2, as well as the noteworthy fortifying effect of the electronically conductive flexible material, graphene. The results provide a promising strategy for its application as an efficient and stable HER catalyst.

Li et al. reported MoS₂-based electrocatalysts for the hydrogen evolution reaction. The superior catalytic activity was ascribed to exposed edge sites, sulfur vacancies, 1T phase, and the effect of graphene.

Application of online to offline teaching mode in the training of non-anesthesiology residents in the department of anesthesiology: a randomized, controlled trial.

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology. Trial design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University. Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups. Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p < 0.01). Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness.

Cough symptoms in children following COVID-19: a single-center retrospective study.

Background: Cough is the most common respiratory symptom in children with mild coronavirus disease 2019 (COVID-19); however, evidence regarding the duration and severity of COVID-19-related cough is sparse. Herein, we investigated the correlation between cough severity/duration and disease duration in children with allergic diseases following COVID-19. Methods: This single-center, retrospective case-control study was conducted at the Department of Pediatrics, Peking University Third Hospital, from February 6-13, 2023. Children aged 0-16 completed a questionnaire survey collecting basic information and weekly cough scores for 8 consecutive weeks after COVID-19 in December 2022. The Kaplan-Meier method was used to draw event curves, and the log-rank method was used to compare inter-group differences. Stepwise regression was applied for multivariate analysis of correlations between age, sex, allergic diseases, and the degree and duration of cough following COVID-19. Results: Overall, 686 children were included, of whom 183 (26.7%) had allergic diseases and 503 (73.3%) did not. Kaplan-Meier analysis identified significant differences between patients with and without allergic disease (log-rank test, P = 0.002) and between patients with no allergic disease and those with one and more than one allergic disease (log-rank test, P = 0.003). Multivariate regression identified a link between the presence of more than one allergic disease and coughing for >4 weeks after infection (P < 0.001). Allergic disease was the primary factor linked to cough symptoms lasting 8 weeks and cough severity (P < 0.001). Conclusions: Allergic disease contributes to the prolonged duration and severity of coughing in children with mild COVID-19.

New approach for near-infrared wavelength selection using a combination of MIC and firefly evolution.

Full-length spectral data analysis has a big problem that the variables are highly in collinearity and correlation. Spectral wavelength selection is a continuing hot topic in quantitative or qualitative analysis. In this paper, we propose a new approach for near-infrared (NIR) wavelength selection. The novel strategy mainly refers to the modification of maximum information coefficient (MIC) method and an improvement of firefly evolutionary algorithm. We introduce the orthogonal decomposition to modify the MIC method, so as to search the informative signals conceived in projection vectors. We also raise the common firefly algorithm (FA) as in the discretized mode, and design a novel adaptive mapping function to improve its intelligent computing effect. In experiment, the modified MIC (MICm) method and the adaptive discrete FA algorithm (DFAadp) are joint together for combined optimization of the NIR calibration model. The proposed combined modeling strategy is applied for quantitative analysis of the fishmeal samples, in the concern to select their informative variables/wavelengths. Experimental results indicate that the combination of MICm and DFAadp perform better than traditional MIC method and common DFA. We conclude that the proposed combined optimization strategy is beneficial for wavelength selection in NIR spectral analysis. It is anticipated to be validated for further applications in a wide range.

Tetramerization is essential for the enzymatic function of the Pseudomonas aeruginosa virulence factor UDP-glucose pyrophosphorylase.

Multidrug-resistant bacteria such as the opportunistic pathogen Pseudomonas aeruginosa, which causes life-threatening infections especially in immunocompromised individuals and cystic fibrosis patients, pose an increasing threat to public health. In the search for new treatment options, P. aeruginosa uridine diphosphate-glucose pyrophosphorylase (PaUGP) has been proposed as a novel drug target because it is required for the biosynthesis of important virulence factors and linked to pathogenicity in animal models. Here, we show that UGP-deficient P. aeruginosa exhibits severely reduced virulence against human lung tissue and cells, emphasizing the enzyme's suitability as a drug target. To establish a basis for the development of selective PaUGP inhibitors, we solved the product-bound crystal structure of tetrameric PaUGP and conducted a comprehensive structure-function analysis, identifying key residues at two different molecular interfaces that are essential for tetramer integrity and catalytic activity and demonstrating that tetramerization is pivotal for PaUGP function. Importantly, we show that part of the PaUGP oligomerization interface is uniquely conserved across bacterial UGPs but does not exist in the human enzyme, therefore representing an allosteric site that may be targeted to selectively inhibit bacterial UGPs.IMPORTANCEInfections with the opportunistic bacterial pathogen Pseudomonas aeruginosa are becoming increasingly difficult to treat due to multidrug resistance. Here, we show that the enzyme uridine diphosphate-glucose pyrophosphorylase (UGP) is involved in P. aeruginosa virulence toward human lung tissue and cells, making it a potential target for the development of new antibacterial drugs. Our exploration of P. aeruginosa (Pa)UGP structure-function relationships reveals that the activity of PaUGP depends on the formation of a tetrameric enzyme complex. We found that a molecular interface involved in tetramer formation is conserved in all bacterial UGPs but not in the human enzyme, and therefore hypothesize that it provides an ideal point of attack to selectively inhibit bacterial UGPs and exploit them as drug targets.

Artificial intelligence-driven microbiome data analysis for estimation of postmortem interval and crime location.

Microbial communities, demonstrating dynamic changes in cadavers and the surroundings, provide invaluable insights for forensic investigations. Conventional methodologies for microbiome sequencing data analysis face obstacles due to subjectivity and inefficiency. Artificial Intelligence (AI) presents an efficient and accurate tool, with the ability to autonomously process and analyze high-throughput data, and assimilate multi-omics data, encompassing metagenomics, transcriptomics, and proteomics. This facilitates accurate and efficient estimation of the postmortem interval (PMI), detection of crime location, and elucidation of microbial functionalities. This review presents an overview of microorganisms from cadavers and crime scenes, emphasizes the importance of microbiome, and summarizes the application of AI in high-throughput microbiome data processing in forensic microbiology.

Decoherence-free-subspace-based deterministic conversions for entangled states with heralded robust-fidelity quantum gates.

The decoherence-free subspace (DFS) serves as a protective shield against certain types of environmental noise, allowing the system to remain coherent for extended periods of time. In this paper, we propose two protocols, i.e., one converts two-logic-qubit Knill-Laflamme-Milburn (KLM) state to two-logic-qubit Bell states, and the other converts three-logic-qubit KLM state to three-logic-qubit Greenberger-Horne-Zeilinger states, through cavity-assisted interaction in DFS. Especially, our innovative protocols achieve their objectives in a heralded way, thus enhancing experimental accessibility. Moreover, single photon detectors are incorporated into the setup, which can predict potential failures and ensure seamless interaction between the nitrogen-vacancy center and photons. Rigorous analyses and evaluations of two schemes demonstrate their abilities to achieve near-unit fidelities in principle and exceptional efficiencies. Further, our protocols offer progressive solutions to the challenges posed by decoherence, providing a pathway towards practical quantum technologies.

Radical-Smiles Rearrangement by a Vitamin B2-Derived Photocatalyst in Water.

Herein, we report a catalytic radical-Smiles rearrangement system of arene migration from ether to carboxylic acid with riboflavin tetraacetate (RFT), a readily available ester of natural vitamin B2, as the photocatalyst and water as a green solvent, being free of external oxidant, base, metal, inert gas protection, and lengthy reaction time. Not only the known substituted 2-phenyloxybenzoic acids substrates but also a group of naphthalene- and heterocycle-based analogues was converted to the corresponding aryl salicylates for the first time. Mechanistic studies, especially a couple of kinetic isotope effect (KIE) experiments, suggested a sequential electron transfer-proton transfer processes enabled by the bifunctional flavin photocatalyst.

Alkyne Oxidation by a Vitamin B2-Based Photocatalytic System with Both H2O and O2 as the Oxygen Source.

The employment of readily available photocatalysts and green oxygen atom sources is recognized as a promising strategy to develop sustainable catalysis for oxidation reactions. We herein reported a sacrificial reagent-free system consisting of riboflavin tetraacetate (RFT), an ester of natural vitamin B2 as the photocatalyst, and Sc(OTf)3 and NaCl as the cocatalysts for alkyne oxidation under blue light or even sunlight irradiation to produce 1,2-diketone in which the oxygen atoms were from both water and molecular oxygen, respectively. A major Cl-/Cl• cycle was proposed to be involved and achieved by the excited [RFT-2Sc3+]* complex via single electron transfer for the first time, distinguished from the OCl- active species by a two-electron process in previous flavin-halide photo-oxidation systems.

[Salvianolic acid A contributes to cartilage endplate cell restoration by regulating miR-940 and miR-576-5p].

OBJECTIVE: To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA. METHODS: Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1ß (IL-1ß)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs. RESULTS: The 10 µM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1ß, and reduced the effect of IL-1ß on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs. CONCLUSION: Salvianolic acid A attenuated the IL-1ß-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.

Traditional Chinese Medicine formula Bu-Shen-Huo-Xue-Fang (BSHXF) protects nucleus pulposus cells against the inflammatory and oxidative stress-induced degenerative changes.

Degeneration of the intervertebral disc is primarily caused by the loss of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) (IDD). Bu-Shen-Huo-Xue-Fang (BSHXF), a traditional Chinese medicine decoction, has been used to treat IDD in clinical; nevertheless, the active components and underlying molecular mechanisms remain unknown. BSHXF improved IL-1ß and H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The active ingredients in BSHXF were identified by LC-MS/MS analysis; three active ingredients from the principal drugs, Aucubin, Tanshinol, and Tanshinone II A promoted NPC viability; and Aucubin and Tanshinol promoted NPC viability more. Aucubin and Tanshinol, respectively, improved H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The activator of NF-κB and Wnt signaling pathways attenuated Aucubin and Tanshinol's protective effects by promoting ECM degradation and NPC senescence. Aucubin, Tanshinol, and Tanshinone II A were identified as the most potent compounds in BSHXF protection against degenerative changes in NPCs. The NF-κB and Wnt signaling pathways might be involved in the protective effects of Aucubin and Tanshinol against H2O2-induced degenerative changes.

Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: Characterization, neuroprotective effect and in vivo pharmacokinetic study.

Curcumin (CUR) is a natural polyphenol extract with significant antioxidant and anti-inflammatory effects, which indicates its great potential for neuroprotection. Lactoferrin (LF), a commonly used oral carrier and targeting ligand, has not been reported as a multifunctional nanocarrier for nose-to-brain delivery. This study aims to develop a nose-to-brain delivery system of curcumin-lactoferrin nanoparticles (CUR-LF NPs) and to further evaluate the neuroprotective effects in vitro and brain accumulation in vivo. Herein, CUR-LF NPs were prepared by the desolvation method with a particle size of 84.8 ± 6.5 nm and a zeta potential of +22.8 ± 4.3 mV. The permeability coefficient of CUR-LF NPs (4.36 ± 0.79 × 10-6 cm/s) was 50 times higher than that of CUR suspension (0.09 ± 0.04 × 10-6 cm/s) on MDCK monolayer, indicating that the nanoparticles could improve the absorption efficiency of CUR in the nasal cavity. Moreover, CUR-LF NPs showed excellent protection against Aß25-35-induced nerve damage in PC12 cells. In vivo pharmacokinetic studies showed that the brain-targeting efficiency of CUR-LF NPs via IN administration was 248.1%, and the nose-to-brain direct transport percentage was 59.7%. Collectively, nose-to-brain delivery of CUR-LF NPs is capable of achieving superior brain enrichment and potential neuroprotective effects.

Immunohistochemical Features of MMP-9 and pSTAT1 in Granuloma Annulare and Sarcoidosis: A Comparative Study of 62 Cases.

Background: Granuloma annulare (GA) and sarcoidosis are granulomatous inflammatory diseases that share similarities. Objective: To identify the histological and immunohistochemical (IHC) features of GA and sarcoidosis. Methods: A retrospective review of 36 patients with GA and 26 with sarcoidosis was performed. Results from hematoxylin and eosin (H&E) staining and IHC staining of MMP-9 and pSTAT1 within the skin lesions of GA and sarcoidosis were analyzed, and random forest was applied for developing a predictive model. Results: Significantly greater expressions of MMP-9 (especially in elastic fibers, EFs, P < 0.0001) and pSTAT1 (P = 0.0003) were observed in lesion samples of GA versus sarcoidosis patients. In GA patients, MMP-9 was significantly upregulated in the interstitial type (P = 0.0222), while staining of pSTAT1 was positively correlated with the area of mucinous collagen in palisading GA (R = 0.5356, P = 0.0484). In sarcoidosis patients, MMP-9 (R = -0.7127, P = 0.0009) and pSTAT1 (R = -0.5604, P = 0.0067) were found to show stronger expressions in lesions with less lymphocyte infiltration. The predictive model demonstrated an AUC of 0.9675. Conclusion: These results indicate that MMP-9 and pSTAT1 might exert roles in granulomatous inflammation in different modes, and the presence of more robust MMP-9 staining in EFs appears to be more suggestive of GA.