Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.

Engineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR-Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors. We used these components to construct potent and compact multipartite transactivation modules (MSN, NMS and eN3x9) and to build the CRISPR-dCas9 recruited enhanced activation module (CRISPR-DREAM) platform. We found that CRISPR-DREAM was specific and robust across mammalian cell types, and efficiently stimulated transcription from diverse regulatory loci. We also showed that MSN and NMS were portable across Type I, II and V CRISPR systems, transcription activator-like effectors and zinc finger proteins. Further, as proofs of concept, we used dCas9-NMS to efficiently reprogram human fibroblasts into induced pluripotent stem cells and demonstrated that mechanosensitive transcription factor TADs are efficacious and well tolerated in therapeutically important primary human cell types. Finally, we leveraged the compact and potent features of these engineered TADs to build dual and all-in-one CRISPRa AAV systems. Altogether, these compact human TADs, fusion modules and delivery architectures should be valuable for synthetic transcriptional control in biomedical applications.

Database resources of the National Center for Biotechnology Information.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, SciENcv, the NIH Comparative Genomics Resource (CGR), NCBI Virus, SRA, RefSeq, foreign contamination screening tools, Taxonomy, iCn3D, ClinVar, GTR, MedGen, dbSNP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

PubChem 2023 update.

PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves a wide range of use cases. In the past two years, a number of changes were made to PubChem. Data from more than 120 data sources was added to PubChem. Some major highlights include: the integration of Google Patents data into PubChem, which greatly expanded the coverage of the PubChem Patent data collection; the creation of the Cell Line and Taxonomy data collections, which provide quick and easy access to chemical information for a given cell line and taxon, respectively; and the update of the bioassay data model. In addition, new functionalities were added to the PubChem programmatic access protocols, PUG-REST and PUG-View, including support for target-centric data download for a given protein, gene, pathway, cell line, and taxon and the addition of the 'standardize' option to PUG-REST, which returns the standardized form of an input chemical structure. A significant update was also made to PubChemRDF. The present paper provides an overview of these changes.

Database resources of the National Center for Biotechnology Information in 2023.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. New resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, IgBLAST, GDV, RefSeq, NCBI Virus, GenBank type assemblies, iCn3D, ClinVar, GTR, dbGaP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

Adaptive Gap-Tunable Surface-Enhanced Raman Spectroscopy.

Gap plasmon (GP) resonance in static surface-enhanced Raman spectroscopy (SERS) structures is generally too narrow and not tunable. Here, we present an adaptive gap-tunable SERS device to selectively enhance and modulate different vibrational modes via active flexible Au nanogaps, with adaptive optical control. The tunability of GP resonance is up to ∼1200 cm-1 by engineering gap width, facilitated by mechanical bending of a polyethylene terephthalate substrate. We confirm that the tuned GP resonance selectively enhances different Raman spectral regions of the molecules. Additionally, we dynamically control the SERS intensity through the wavefront shaping of excitation beams. Furthermore, we demonstrate simulation results, exhibiting the mechanical and optical properties of a one-dimensional flexible nanogap and their advantage in high-speed biomedical sensing. Our work provides a unique approach for observing and controlling the enhanced chemical responses with dynamic tunability.

Reducing cost in DNA-based data storage by sequence analysis-aided soft information decoding of variable-length reads.

MOTIVATION: DNA-based data storage is one of the most attractive research areas for future archival storage. However, it faces the problems of high writing and reading costs for practical use. There have been many efforts to resolve this problem, but existing schemes are not fully suitable for DNA-based data storage, and more cost reduction is needed. RESULTS: We propose whole encoding and decoding procedures for DNA storage. The encoding procedure consists of a carefully designed single low-density parity-check code as an inter-oligo code, which corrects errors and dropouts efficiently. We apply new clustering and alignment methods that operate on variable-length reads to aid the decoding performance. We use edit distance and quality scores during the sequence analysis-aided decoding procedure, which can discard abnormal reads and utilize high-quality soft information. We store 548.83 KB of an image file in DNA oligos and achieve a writing cost reduction of 7.46% and a significant reading cost reduction of 26.57% and 19.41% compared with the two previous works. AVAILABILITY AND IMPLEMENTATION: Data and codes for all the algorithms proposed in this study are available at: https://github.com/sjpark0905/DNA-LDPC-codes.

Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson's disease.

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Database resources of the national center for biotechnology information.

The National Center for Biotechnology Information (NCBI) produces a variety of online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for the most of these databases. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, RefSeq, SRA, Virus, dbSNP, dbVar, ClinicalTrials.gov, MMDB, iCn3D and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

Impact of inhalation exposure to cigarette smoke on the pathogenesis of pulmonary hypertension primed by monocrotaline in rats.

Extensive, long-term exposure to cigarette smoke (CS) was recently suggested to be a risk factor for pulmonary hypertension, although further validation is required. The vascular effects of CS share similarities with the etiology of pulmonary hypertension, including vascular inflammation and remodeling. Thus, we examined the influence of CS exposure on the pathogenesis of monocrotaline (MCT)-induced pulmonary hypertension, hypothesizing that smoking might accelerate the development of primed pulmonary hypertension. CS was generated from 3R4F reference cigarettes, and rats were exposed to CS by inhalation at total particulate matter concentrations of 100-300 µg/L for 4 h/day, 7 days/week for 4 weeks. Following 1 week of initial exposure, rats received 60 mg/kg MCT and were sacrificed and analyzed after an additional 3 weeks of exposure. MCT induced hypertrophy in pulmonary arterioles and increased the Fulton index, a measure of right ventricular hypertrophy. Additional CS exposure exacerbated arteriolar hypertrophy but did not further elevate the Fulton index. No significant alterations were observed in levels of endothelin-1 and vascular endothelial growth factor, or in hematological and serum biochemical parameters. Short-term inhalation exposure to CS exacerbated arteriolar hypertrophy in the lung, although this effect did not directly aggravate the overworked heart under the current experimental conditions.

The posterior tibial slope affects the measurement reliability regarding the radiographic parameter of the knee.

BACKGROUND: Posterior tibial slope (PTS) exhibits considerable variability among individuals and is anticipated to influence the accuracy of radiographic measurements related to the knee. Despite this potential impact, there is a lack of prior research investigating how PTS affects the accuracy of these measurements. Therefore, this study aimed to investigate the effect of PTS on the measurement reliability regarding the radiographic parameter of the knee. METHODS: The medical records of patients who took full-length anteroposterior radiographs of the lower limb between January 2020 and June 2022 were evaluated retrospectively. Radiographic parameters related to the knee joint characteristics such as osteoarthritis grade, hip-knee-ankle angle, weight-bearing line ratio, medial proximal tibial angle (MPTA), lateral distal femoral angle, joint-line convergence angle (JLCA), and PTS were measured. Subjects were classified into 3 groups according to PTS (group A, PTS < 4°; group B, PTS ≥ 4° and < 8°; group C, PTS ≥ 8°), and the measurement reliability for the radiographic variables was compared between groups. The intra- and inter-observer agreements were assessed using the kappa coefficients, intra-class correlation coefficients (ICC), and Bland-Altman plots. RESULTS: A total of 175 limbs (86 patients) were included in this study. As the intra- and inter-observer reliability for PTS ranged over 0.9, grouping was performed based on the average of the measured PTSs. The inter-observer reliability of the MPTA and JLCA decreased as the PTS increased (ICCs for MPTA in Groups A, B, and C: 0.889, 0.796, and 0.790, respectively; ICCs for JLCA in Groups A, B and C: 0.916, 0.859, and 0.843, respectively), whereas there were no remarkable differences in other variables. Similar trends were observed in the comparisons of intra-observer reliability and Bland-Altman plots also showed consistent results. CONCLUSION: The larger the PTS, the lower the measurement reliability regarding the radiographic parameters of the knee that includes the joint line, such as MPTA and JLCA. Given the occasional challenge in accurately identifying the knee joint line in patients with a relatively large PTS, careful measurement of radiographic parameters is crucial and utilizing repetitive measurements for verification may contribute to minimizing measurement errors.

Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

BACKGROUND: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION: This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Release or transection of superficial medial collateral ligament during open-wedge high tibial osteotomy demonstrated similar clinical outcomes and valgus laxity.

PURPOSE: To analyse whether valgus laxity and clinical outcomes differ depending on whether the superficial medial collateral ligament (sMCL) is released or transected during medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Consecutive patients who underwent MOWHTO and subsequent radiological follow-up for at least 2 years were retrospectively evaluated. The patients were divided into release and transection groups, according to the sMCL manipulation technique. Each patient was assessed for the following variables on valgus stress radiographs taken before surgery and at the 12- and 24-month follow-ups: the absolute value of valgus (ABV) and side-to-side difference (SSD) between the affected and normal sides. The differences between preoperative SSD and those at 12 and 24 months were respectively calculated and defined as delta SSD (ΔSSD). The Visual Analogue Scale, Lysholm knee, International Knee Documentation Committee subjective, and Knee Injury and Osteoarthritis Outcome scores were used to evaluate patient-reported outcomes. RESULTS: Eighty-five patients were included in the study. Forty-two patients (49.6%) underwent sMCL release, and the remaining 43 patients (50.4%) underwent sMCL transection. No significant differences were observed in the ABV and SSD of valgus laxity at the different time points between the two groups (n.s.). Furthermore, no significant differences were observed in the ΔSSD at the 12- and 24-month follow-ups between the two groups (n.s.). Significant improvement from preoperative values was observed in all patient-reported outcomes (p < 0.001), with no significant differences between the two groups at any time point (n.s.). CONCLUSION: Significant improvements in clinical outcomes were observed, regardless of the technique used. Postoperative valgus laxity did not occur with either technique. The transection technique, which can be performed more simply and quickly, demonstrated similar clinical outcomes and valgus laxity to the release technique. LEVEL OF EVIDENCE: Level III.

Patellofemoral joint cartilage lesions frequently develop shortly after anterior cruciate ligament reconstruction using hamstring tendon autograft: A systematic review.

PURPOSE: This study aimed to investigate the development of patellofemoral joint (PFJ) cartilage lesions following anterior cruciate ligament reconstruction (ACLR) using hamstring tendon (HT) autograft through a systematic review. METHODS: A comprehensive search was conducted in PubMed, Embase, Cochrane Library and Google Scholar databases to find articles published from database inception until 15 November 2023. The search terms were [('Anterior Cruciate Ligament' [mesh] OR 'anterior cruciate ligament' OR 'ACL') AND 'reconstruction' AND 'cartilage' AND ('second look arthroscopy' OR 'second-look arthroscopy' OR 'MRI' OR 'magnetic resonance imaging')]. Inclusion criteria were studies that reported on the occurrence of PFJ cartilage lesions following ACLR using HT autograft, as determined by second-look arthroscopy or follow-up magnetic resonance imaging (MRI). RESULTS: Fifteen studies (1084 patients) met the inclusion criteria, with follow-up periods ranging from 1 to 5 years. In the results of second-look arthroscopy, cartilage grade deterioration was observed, ranging from MDs of 0.1 to 2.0 in the patella and from 0 to 1.0 in the trochlea. Follow-up MRI results reported the incidence of PFJ cartilage degeneration with rates ranging from 20% to 44%. Patient-reported outcome measures often showed no significant association with PFJ cartilage lesions. The studies included in this review reported various risk factors for cartilage lesion development. CONCLUSION: Cartilage lesions in the PFJ, detected using second-look arthroscopy or follow-up MRI, frequently develop shortly after ACLR using HT autograft. At this stage, patients might not show specific symptoms; however, those with risk factors require careful observation and evaluation by clinicians during follow-up. LEVEL OF EVIDENCE: Level IV.

Preoperative joint line obliquity, a newly identified factor for overcorrection, can be incorporated into a novel preoperative planning method to optimise alignment in high tibial osteotomy.

PURPOSE: The aim of this study was to analyse the factors associated with additional postoperative alignment changes after accurate bony correction by selecting only patients with well-performed bony correction as planned and develop a method of incorporating significant factors into preoperative planning. METHODS: Among 104 consecutive patients who underwent medial open wedge high tibial osteotomy (MOWHTO) between October 2019 and July 2022, 61 with well-performed bony corrections were retrospectively reviewed. The major criterion for well-performed bony correction was a difference of <1° between the simulated medial proximal tibial angle (MPTA) and the actual postoperative MPTA as measured in three dimensions. Radiographic parameters, such as the joint line convergence angle (JLCA) and joint line obliquity (JLO), were measured preoperatively and postoperatively, utilising standing and supine whole lower extremity anteroposterior, valgus and varus stress radiographs. Multiple linear regression analysis identified the factors affecting alignment changes, and a prediction model was developed. A method for applying this prediction model to preoperative planning was proposed. RESULTS: Preoperative JLCA on standing (preJLCAstd ), preoperative JLCA on 0° valgus stress radiograph (vgJLCA0 ), and preoperative JLO (preJLO) were significantly correlated with JLCA change (∆JLCA) (p < 0.001, p < 0.001, p = 0.006). The prediction model was estimated as ∆JLCA = 0.493 × (vgJLCA0 ) - 0.727 × (preJLCAstd ) + 0.189 × (preJLO) - 1.587 in. (R = 0.815, modified R2 = 0.646, p < 0.001). The proposed method resulted in a reduced overcorrection rate (p = 0.003) and an improved proportion of acceptable alignments (p = 0.013). CONCLUSION: PreJLCAstd , vgJLCA0  and preJLO can be used to estimate ∆JLCA. PreJLO was recently identified as a significant factor associated with additional alignment changes. Utilising the proposed preoperative planning and a prediction model with these factors shows promise in calibrating postoperative alignment after MOWHTO. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.

Biological activities, identification, method development, and validation for analysis of polyphenolic compounds in Nymphaea rubra flowers and leaves by UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS.

INTRODUCTION: Nymphaea rubra belongs to the Nymphaea family and is regarded as a vegetable used in traditional medicine to cure several ailments. These species are rich in phenolic acid, flavonoids, and hydrolysable tannin. OBJECTIVE: This study aimed to assess the biological activities of Nymphaea rubra flowers (NRF) and leaves (NRL) by identifying and quantifying their polyphenolic compounds using ultra-performance liquid chromatography coupled to quadrupole cyclic ion mobility time-of-flight mass spectrometry (UHPLC-Q-cIM-TOF-MS) and triple quadrupole mass spectrometry (UHPLC-TQ-MS). METHODOLOGY: NRF and NRL powder was extracted with methanol and fractionated using hexane, ethylacetate, and water. Antioxidant and α-glucosidase, and tyrosinase enzyme inhibitory activities were evaluated. The polyphenolic components of NRF and NRL were identified and quantified using UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS. The method was validated using linearity, precision, accuracy, limit of detection (LOD), and lower limit of quantification (LLOQ). RESULTS: Bioactive substances and antioxidants were highest in the ethylacetate fraction of flowers and leaves. Principal component analysis showed how solvent and plant components affect N. rubra's bioactivity and bioactive compound extraction. A total of 67 compounds were identified, and among them 21 significant polyphenols were quantified. Each calibration curve had R2 > 0.998. The LOD and LLOQ varied from 0.007 to 0.09 µg/mL and from 0.01 to 0.1 µg/mL, respectively. NRF contained a significant amount of gallic acid (10.1 mg/g), while NRL contained abundant pentagalloylglucose (2.8 mg/g). CONCLUSION: The developed method is simple, rapid, and selective for the identification and quantification of bioactive molecules. These findings provide a scientific basis for N. rubra's well-documented biological effects.

Development of a prediction model for cognitive impairment of sarcopenia using multimodal neuroimaging in non-demented older adults.

INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non-demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit-to-stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid-beta (Aß) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aß retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub-domain of sarcopenia should be considered to prevent cognitive decline. HIGHLIGHTS: We identified distinct impacts of three sarcopenia measures on brain structure and Aß. Muscle mass is mainly associated with Aß and has an influence on the brain atrophy. Muscle strength linked with periventricular WMH and brain atrophy. Muscle function associated with cortical thinning in specific brain regions. Interventions on sarcopenia may be important to ease cognitive decline in the elderly.

The effects of Pycnogenol, a pine bark extract on pulmonary inflammation by Asian sand dust in mice.

Asian sand dust (ASD), also called China dust or yellow dust, mainly occurs in East Asia during spring and autumn. Because ASD enters the body mainly through the respiratory system, it can cause respiratory disorders or worsen underlying diseases. Because of this, it has become an important health concern that threatens the well-being of humans and animals. In this study, we investigated the effects of 15 and 30 mg/kg of Pycnogenol (PYC15 and 30 groups), a pine bark extract, on ASD-induced pulmonary inflammation in mice. We evaluated the inflammatory cell counts, inflammatory cytokines, and matrix-metalloproteinase (MMP)-9 expression in animal models. PYC administration significantly decreased inflammatory cell infiltration into lung tissue; this was accompanied by a reduction in the levels of proinflammatory mediators including interleukin (IL)-1ß (P < 0.01), IL-6 (P < 0.01) and tumour necrosis factor-α (P < 0.01) in bronchoalveolar lavage fluids of ASD-exposed mice (ASD group). Histological analysis revealed that PYC suppressed ASD-induced pulmonary inflammation. Moreover, PYC suppressed the levels of matrix-metalloproteinase (MMP)-9 in the lung tissue of ASD-exposed mice, indicating that PYC reduced ASD-induced pulmonary inflammation by suppressing MMP-9. Together, these results indicate that PYC as the potential to treat ASD-driven pulmonary inflammation.

Palsy of Both the Tibial Nerve and Common Peroneal Nerve Caused by a Ganglion Cyst in the Popliteal Area.

A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient's neurological symptoms improved. There was no recurrence.

Analysis of environmental organic matters by Ultrahigh-Resolution mass spectrometry-A review on the development of analytical methods.

Owing to the increasing environmental and climate changes globally, there is an increasing interest in the molecular-level understanding of environmental organic compound mixtures, that is, the pursuit of complete and detailed knowledge of the chemical compositions and related chemical reactions. Environmental organic molecule mixtures, including those in air, soil, rivers, and oceans, have extremely complex and heterogeneous chemical compositions. For their analyses, ultrahigh-resolution and sub-ppb level mass accuracy, achievable using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), are important. FT-ICR MS has been successfully used to analyze complex environmental organic molecule mixtures such as natural, soil, particulate, and dissolved organic matter. Despite its success, many limitations still need to be overcome. Sample preparation, ionization, structural identification, chromatographic separation, and data interpretation are some key areas that have been the focus of numerous studies. This review describes key developments in analytical techniques in these areas to aid researchers seeking to start or continue investigations for the molecular-level understanding of environmental organic compound mixtures.