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Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Abstract Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient’s quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.

Preserving fungal tissue DNA in the field is essential for molecular ecological research, enabling the study of fungal biodiversity and community dynamics. This study systematically compares two liquid-based preservation solutions, RNAlater and DESS, for their effectiveness in maintaining macrofungi DNA integrity during field collection and storage. The research encompasses both controlled experiments and real-world field collections. In the controlled experiments, two fungal species were preserved in RNAlater and DESS at different temperatures and durations. DNA extraction success rates were high, but DNA quality and quantity metrics exhibited variations across samples. However, both preservation solutions demonstrated their viability for preserving fungal DNA, with no significant differences between them. In the field-collected macrofungi experiment, 160 paired fungal specimens were preserved in RNAlater and DESS, respectively. Including a drying process to facilitate tissue lysis for DNA extraction significantly impacted the outcomes. RNAlater showed a higher success rate and better DNA quality and quantity compared to DESS. Statistical analysis, including paired and independent t-tests, confirmed significant differences in DNA quality and quantity between the two preservation methods for field-collected samples. This study evaluates RNAlater and DESS for preserving macrofungi DNA in field conditions. Both methods are effective, but RNAlater is superior when a drying step is included in DNA extraction. Researchers can choose based on their specific needs without compromising DNA integrity. These findings advance fungal molecular ecology and DNA preservation strategies in ecological and environmental studies.

Wernicke encephalopathy (WE) is an acute life-threatening neurological condition caused by thiamine (vitamin B1) deficiency. Patients with WE often present with a triad of symptoms consisting of ophthalmoplegia, gait ataxia, and mental confusion. If WE is not treated in a timely manner, it can lead to serious complications such as confusion, coma, or death. Although alcohol abuse is the most commonly reported cause of WE, nonalcoholic causes—although rare—do exist. Herein, we present the case of a nonalcoholic woman with medullary infarctions who presented with intractable vomiting. Her clinical state subsequently progressed to include ophthalmoplegia and gait ataxia. A diagnosis of WE was suspected based on her clinical presentation; this was confirmed by brain magnetic resonance imaging (MRI) and the finding of decreased serum thiamine levels. Brain magnetic resonance imaging demonstrated the complete resolution of abnormal hyperintensities during a follow-up visit, 6 months after treatment.

Abstract Background [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). Methods A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). Results In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). Conclusion The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging.

ObjectiveTangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD).MethodsThe mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction.ResultsMass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-β, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD.ConclusionTBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

BackgroundThis study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions. ObjectiveWe hypothesized that the app-based measurement may provide more comprehensive information, including light-sensitive melatonin secretion and social rhythm, and have stronger correlations with adiposity indicators. MethodsWe enrolled a total of 78 participants (mean age 41.5, SD 9.9 years; 46/78, 59% women) from both an obesity outpatient clinic and a workplace health promotion program. All participants (n=29 with obesity, n=16 overweight, and n=33 controls) were required to wear a wrist actigraphy device and install the Rhythm app for a minimum of 4 weeks, contributing to a total of 2182 person-days of data collection. The Rhythm app estimates sleep and circadian rhythm indicators by tracking human-smartphone interactions, which correspond to actigraphy. We examined the correlations between adiposity indices and sleep and circadian rhythm indicators, including sleep time, chronotype, and regularity of circadian rhythm, while controlling for physical activity level, age, and gender. ResultsSleep onset and wake time measurements did not differ significantly between the app and actigraphy; however, wake after sleep onset was longer (13.5, SD 19.5 minutes) with the app, resulting in a longer actigraphy-measured total sleep time (TST) of 20.2 (SD 66.7) minutes. The obesity group had a significantly longer TST with both methods. App-measured circadian rhythm indicators were significantly lower than their actigraphy-measured counterparts. The obesity group had significantly lower interdaily stability (IS) than the control group with both methods. The multivariable-adjusted model revealed a negative correlation between BMI and app-measured IS (P=.007). Body fat percentage (BF%) and visceral adipose tissue area (VAT) showed significant correlations with both app-measured IS and actigraphy-measured IS. The app-measured midpoint of sleep showed a positive correlation with both BF% and VAT. Actigraphy-measured TST exhibited a positive correlation with BMI, VAT, and BF%, while no significant correlation was found between app-measured TST and either BMI, VAT, or BF%. ConclusionsOur findings suggest that IS is strongly correlated with various adiposity indicators. Further exploration of the role of circadian rhythm, particularly measured through human-smartphone interactions, in obesity prevention could be warranted.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Abstract Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory‐polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein‐based conduits. Moreover, the NGC can gradually regulate the intra‐conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

We report the publication of 953 DNA barcodes of forest leaf litter beetles from central Taiwan, in total representing 334 species of 36 beetle families. This is the first bulk of data from the Taiwanese Leaf Litter beetles project focused on uncovering the under-explored diversity of leaf litter beetles across Taiwan. Based on these data, we provide the first records of the following taxa for Taiwan: family Sphindidae (genus Aspidiphorus Ziegler, 1821); tribes Trichonychini, Ctenistini, and Bythinoplectini (all Staphylinidae: Pselaphinae); genera Gyrelon Hinton, 1942, Thyroderus Sharp, 1885, Cautomus Sharp, 1885 (all Cerylonidae), Dermatohomoeus Hlisnikovský, 1963 (Leiodidae), Paraploderus Herman, 1970 (Staphylinidae: Oxytelinae), Thinocharis Kraatz, 1859 (Staphylinidae: Paederinae), Cephennodes Reitter, 1884, Napoconnus Franz, 1957 (both Staphylinidae: Scydmaeninae), Bicava Belon, 1884 (Latridiidae), Otibazo Morimoto, 1961, Seleuca Pascoe, 1871 and Acallinus Morimoto, 1962 (all Curculionidae); species Oodes (Lachnocrepis) japonicus (Bates, 1873) (Carabidae: Licininae), Drusilla obliqua (Bernhauer, 1916) (Staphylinidae: Aleocharinae) and Coccotrypes advena Blandford, 1894 (Curculionidae: Scolytinae). The records of Anapleus Horn, 1873 (Histeridae) and Batraxis Reitter, 1882 (Staphylinidae: Pselaphinae) have been confirmed. The male of Sivacrypticus taiwanicus Kaszab, 1964 (Archeocrypticidae) is described for the first time. Gyrelon jenpani Hu, Fikáček & Matsumoto, sp. nov. (Cerylonidae) is described, illustrated, and compared with related species. DNA barcodes associated larvae of 42 species with adults, we are concisely illustrating some of these: Oodes japonicus, Perigona cf. nigriceps Dejean, 1831 (both Carabidae), Ptilodactyla sp. (Ptilodactylidae), Maltypus ryukyuanus Wittmer, 1970 (Cantharidae), Drusilla obliqua, Myrmecocephalus brevisulcus (Pace, 2008), Diochus sp., Mimopinophilus sp. (all Staphylinidae), Stelidota multiguttata Reitter, 1877, Lasiodites inaequalis (Grouvelle, 1914) (both Nitidulidae), Lagria scutellaris Pic, 1910, and Anaedus spinicornis Kaszab, 1973 (both Tenebrionidae). We also report the first cases of Rickettsia infections in Scydmaeninae and Pselaphinae. All data (sequences, metadata, and voucher photos) are made public in BOLD database and in a Zenodo Archive.