Standardization and quality assessment for human intestinal organoids.

To enhance the practical application of intestinal organoids, it is imperative to establish standardized guidelines. This proposed standardization outlines a comprehensive framework to ensure consistency and reliability in the development, characterization, and application of intestinal organoids. The recommended guidelines encompass crucial parameters, including culture conditions, critical quality attributes, quality control measures, and functional assessments, aimed at fostering a standardized approach across diverse research initiatives. The implementation of these guidelines is anticipated to significantly contribute to the reproducibility and comparability of results in the burgeoning field of intestinal organoid research.

Spin Hall-induced bilinear magnetoelectric resistance.

Magnetoresistance is a fundamental transport phenomenon that is essential for reading the magnetic states for various information storage, innovative computing and sensor devices. Recent studies have expanded the scope of magnetoresistances to the nonlinear regime, such as a bilinear magnetoelectric resistance (BMER), which is proportional to both electric field and magnetic field. Here we demonstrate that the BMER is a general phenomenon that arises even in three-dimensional systems without explicit momentum-space spin textures. Our theory suggests that the spin Hall effect enables the BMER provided that the magnitudes of spin accumulation at the top and bottom interfaces are not identical. The sign of the BMER follows the sign of the spin Hall effect of heavy metals, thereby evidencing that the BMER originates from the bulk spin Hall effect. Our observation suggests that the BMER serves as a general nonlinear transport characteristic in three-dimensional systems, especially playing a crucial role in antiferromagnetic spintronics.

Stage Evaluation of Cystic Duct Cancer.

Purpose: Cystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs. Materials and Methods: T category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata's classifications (type 1, confined within cystic duct (CD); combined types 2-4, extension beyond CD) and compared them. Results: No significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1-T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1-T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types. Conclusion: Unlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.

Contents of paeoniflorin and albiflorin in two Korean landraces of Paeonia lactiflora and characterization of paeoniflorin biosynthesis genes in peony.

BACKGROUND AND RESEARCH PURPOSE: Paeoniflorin and albiflorin are monoterpene glycosides that exhibit various medicinal properties in Paeonia species. This study explored the terpene biosynthesis pathway and analyzed the distribution of these compounds in different tissues of two Korean landraces of Paeonia lactiflora to gain insights into the biosynthesis of monoterpene glycosides in P. lactiflora and their potential applications. MATERIALS AND METHODS: Two Korean landraces, Hongcheon var. and Hwacheon var, of P. lactiflora were used for the analyses. Contents of the paeoniflorin and albiflorin were analyzed using HPLC. RNA was extracted, sequenced, and subjected to transcriptome analysis. Differential gene expression, KEGG, and GO analyses were performed. Paeoniflorin biosynthesis genes were isolated from the transcriptomes using the genes in Euphorbia maculata with the NBLAST program. Phylogenetic analysis of of 1-Deoxy-D-xylulose 5-phosphate synthase (DOXPS), geranyl pyrophosphate synthase (GPPS), and pinene synthase (PS) was carried out with ClustalW and MEGA v5.0. RESULTS AND DISCUSSION: Analysis of paeoniflorin and albiflorin content in different tissues of the two P. lactiflora landraces revealed significant variation. Transcriptome analysis yielded 36,602 unigenes, most of which were involved in metabolic processes. The DEG analysis revealed tissue-specific expression patterns with correlations between landraces. The isolation of biosynthetic genes identified 173 candidates. Phylogenetic analysis of the key enzymes in these pathways provides insights into their evolutionary relationships. The sequencing and analysis of DOXPS, GPPS, PS revealed distinct clades and subclades, highlighting their evolutionary divergence and functional conservation. Our findings highlight the roots as the primary sites of paeoniflorin and albiflorin accumulation in P. lactiflora, underscoring the importance of tissue-specific gene expression in their biosynthesis. CONCLUSION: this study advances our understanding of monoterpene glycoside production and distribution in Paeonia, thereby guiding further plant biochemistry investigations.

Comparison of Midterm Outcomes between All-Inside Arthroscopic and Open Modified Broström Procedures as Treatment for Chronic Ankle Instability.

Background: Although the all-inside arthroscopic modified Broström operation (AMBO) and open modified Broström operation (OMBO) for chronic lateral ankle instability (CLAI) showed favorable outcomes up to 1-year short-term follow-up, concerns about the long-term stability of AMBO are still present. Therefore, we aimed to compare midterm outcomes between the 2 methods by extending the observation period. Methods: Fifty-four patients undergoing ankle surgery between August 2013 and July 2017 were included in the AMBO (n = 37) and OMBO (n = 17) groups. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale and a visual analog scale (VAS) were used to evaluate the clinical outcomes. Anterior drawer test and talar tilt angle were used to evaluate the radiological outcomes. The mean follow-up duration was 59.69 months. Results: The 2 groups both showed improved clinical and radiological results statistically. In addition, they did not differ in age, sex, or preoperative AOFAS ankle-hindfoot scale score, VAS score, anterior drawer test, or talar tilt angle. No significant difference in the final follow-up postoperative clinical scores or radiological outcomes was observed. Conclusions: AMBO and OMBO as treatments for CLAI did not yield differing clinical or radiological outcomes at a mean follow-up time point of 59.69 months.

Empirical relationship between vadose zone properties and diesel attenuation capacity: A complement for intrinsic vulnerability models.

Evaluating and predicting the natural attenuation capacity (AC) of a vadose zone is essential for determining groundwater vulnerability to contamination from upper sources. However, it remains unclear how the physicochemical properties of vadose zone soils affect AC owing to their complexity and spatial heterogeneity. In this study, we developed a regression model for estimating the AC of a vadose zone against diesel using datasets from different soils with a wide range of physicochemical properties. Among the 17 properties, six (i.e., organic matter (OM), total phosphorous (TP), coefficient of uniformity, particle size (D30), van Genuchten's n, saturation degree (SD)) were selected as primary regressors. The results indicate that biogeochemical factors, including OM and TP, have decisive effects on the AC. Finally, the regression model was expanded to a GIS-based spatial model and applied to Namyangju, Korea using the index-overlay method. The produced AC map showed a nonmonotonic decrease along the depth, and the areas closer to the water bodies generally represented low AC values, most likely due to the lower OM, TP, and higher SD. This study provides an empirical basis for future research initiatives for spatial and temporal AC dynamics, which complements conventional intrinsic groundwater vulnerability models such as DRASTIC.

SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.

The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.

A Case Study of Stress-Induced Alopecia Areata Treated with Hominis Placenta Pharmacopunture.

The purpose of this study is to report the clinical application of Hominis Placenta Pharmacopunture for Alopecia areata. Patient was diagnosed as stress-induced Alopecia areata 1 years ago. To reduce symptom, we treated a patient 8 times using Hominis Placenta Pharmacopunture. Hominis Placenta was injected subcutaneously into the lesion of head scalp alopecia. According to photographs, the lesion had been replaced with new terminal hair and the size of the lesion had decreased. This case has shown that stress-induced Alopecia areata patient could be treated by Hominis Placenta Pharmacopunture.

The "Swing-Door" Regrafting of Donor Site: An Alternative Method for Split-Thickness Skin Graft in the Hand.

Background Skin defects in the hands are common injuries, and autologous skin grafting is the ideal treatment. However, complications can occur at the donor and recipient sites. This study compares the "Swing-door" technique with conventional skin grafting. Methods From August 2019 to February 2023, 19 patients with skin defects of hand underwent the "Swing-door" split-thickness skin graft (STSG) technique. The thin epithelial layer was elevated with proximal part attached. Skin graft was harvested beneath. Donor site was then closed with epithelial flap like a "Swing-door". The outcomes were evaluated in terms of healing time, scar formation, and pain at the donor and recipient sites. The data were compared with the conventional STSG. Results The "Swing-door" group had lower graft take percentages, but complications did not significantly differ between the two groups. The "Swing-door" technique resulted in better cosmetic outcomes, as evidenced by lower Vancouver Scar Scale scores, faster donor site epithelialization, and reduced pain and discomfort during the early postoperative period, as measured by Visual Analog Scale. Conclusion The "Swing-door" STSG is a useful alternative for treating hand skin defects.

Serious Complications of the Percutaneous A1 Pulley Release: Case Reports and Literature Review.

Percutaneous first annular pulley (A1 pulley) release, which has been increasingly used to treat trigger fingers, has been widely established as a safe and simple procedure. Multiple studies have reported positive results of percutaneous A1 pulley release. In this study, however, we report cases of patients who developed complications after undergoing percutaneous A1 pulley release at local clinics. A total of six patients visited our hospital for infectious complications after percutaneous A1 pulley release. Various sequelae such as damage to normal structures, insufficient procedure, and tissue necrosis were observed during the exploration. A retrospective study was conducted to identify the cause and trend of the observed complications by instruments (HAKI knife or needle). In the HAKI knife group, there was a tendency for damage to normal structures, while in the needle group, an insufficient release or serious soft tissue necrosis was observed. Based on these cases, our findings confirm the existence and characteristics of infectious complications following the percutaneous A1 pulley release. We further identify that the type of instrument used predicts the nature of complications. Thus, reliable and skilled performance of the procedure by experts is essential for safe treatment.

Hand Reconstruction Using Anterolateral Thigh Free Flap by Terminal Perforator-to-Digital Artery Anastomosis: Retrospective Analysis.

This study aimed to analyze cases of anterolateral thigh (ALT) free flap used for hand reconstruction with terminal perforator-to-digital artery anastomosis. Patients who underwent ALT free flap placement with terminal perforator-to-digital artery anastomosis for hand reconstruction between January 2011 and August 2021 were included. The number, length, and diameter of the perforators and veins, flap size, and operative time were investigated through a retrospective review of charts and photographs. The occurrences of arterial thrombosis, venous thrombosis, arterial spasm, and flap necrosis were analyzed. In total, 50 patients were included in this study. The mean diameter and length of the perforators were 0.68 mm and 3.25 cm, respectively, and the mean number of veins anastomosed was 1.88, with a mean diameter of 0.54 mm. Complications included four cases of arterial thrombosis, one case of venous thrombosis, seven cases of partial necrosis, and one case of total flap failure. Regression analysis showed that a longer perforator was associated with arterial thrombosis whereas larger flap size and number of anastomosed veins were associated with partial necrosis ( p < 0.05). The terminal perforator-to-digital artery anastomosis offers advantages in using compact free flaps with short pedicle lengths to cover small hand defects.

Malignant potential of neuroendocrine microtumor of the pancreas harboring high-grade transformation: lesson learned from a patient with von Hippel-Lindau syndrome.

Pancreatic neuroendocrine microtumor (PNEMT) is a neuroendocrine tumor (NET) < 0.5 cm in diameter, and it is considered benign. We report a PNEMT with high-grade transformation (HGT). A man in his 60s with von Hippel-Lindau syndrome underwent surgical resection of a NET. A second sub-centimeter nodule with a nodule-in-nodule pattern was discovered. The 0.4 cm outer nodule contained clear columnar cells with round nuclei and indistinct nucleoli, while the 0.1 cm inner nodule had eosinophilic cells with an increased nuclear to cytoplasmic ratio, vesicular nuclei, and prominent nucleoli. Tumor cells in the outer and inner nodules were synaptophysin and chromogranin positive. Only the inner nodule was p53 positive, while the outer nodule was exclusively positive for carbonic anhydrase 9 and vimentin. The Ki-67 labeling indices for the outer and inner nodules were 2.1% (grade 1) and 44.3% (grade 3), respectively. This nodule was determined to be a PNEMT with HGT. Our findings suggest that a PNEMT may not always be benign and can undergo HGT.

Fabrication of Zigzag Parylene Nanofibers in Liquid Crystals with Electric Field-Induced Defect Structures.

Liquid crystals (LCs) have been adopted to induce tunable physical properties that dynamically originated from their unique intrinsic properties responding to external stimuli, such as surface anchoring condition and applied electric field, which enables them to be the template for aligning functional guest materials. We fabricate the fiber array from the electrically modulated (in-plain) nematic LC template using the chemical vapor polymerization (CVP) method. Under an electric field, an induced defect structure with a winding number of -1/2 contains a periodic zigzag disclination line. It is known that LC defect structures can trap the guest materials, such as particles and chemicals. However, the resulting fibers grow along the LC directors, not trapped in the defects. To show the versatility of our platform, nanofibers are fabricated on patterned electrodes representing the alphabets 'CVP.' In addition, the semifluorinated moieties are added to fibers to provide a hydrophobic surface. The resultant orientation-controlled fibers will be used in controllable smart surfaces that can be used in sensors, electronics, photonics, and biomimetic surfaces.

Field-free spin-orbit torque switching in ferromagnetic trilayers at sub-ns timescales.

Current-induced spin torques enable the electrical control of the magnetization with low energy consumption. Conventional magnetic random access memory (MRAM) devices rely on spin-transfer torque (STT), this however limits MRAM applications because of the nanoseconds incubation delay and associated endurance issues. A potential alternative to STT is spin-orbit torque (SOT). However, for practical, high-speed SOT devices, it must satisfy three conditions simultaneously, i.e., field-free switching at short current pulses, short incubation delay, and low switching current. Here, we demonstrate field-free SOT switching at sub-ns timescales in a CoFeB/Ti/CoFeB ferromagnetic trilayer, which satisfies all three conditions. In this trilayer, the bottom magnetic layer or its interface generates spin currents with polarizations in both in-plane and out-of-plane components. The in-plane component reduces the incubation time, while the out-of-plane component realizes field-free switching at a low current. Our results offer a field-free SOT solution for energy-efficient scalable MRAM applications.

Field-free switching of perpendicular magnetization by two-dimensional PtTe2/WTe2 van der Waals heterostructures with high spin Hall conductivity.

The key challenge of spin-orbit torque applications lies in exploring an excellent spin source capable of generating out-of-plane spins while exhibiting high spin Hall conductivity. Here we combine PtTe2 for high spin conductivity and WTe2 for low crystal symmetry to satisfy the above requirements. The PtTe2/WTe2 bilayers exhibit a high in-plane spin Hall conductivity σs,y ≈ 2.32 × 105 × h/2e Ω-1 m-1 and out-of-plane spin Hall conductivity σs,z ≈ 0.25 × 105 × h/2e Ω-1 m-1, where h is the reduced Planck's constant and e is the value of the elementary charge. The out-of-plane spins in PtTe2/WTe2 bilayers enable the deterministic switching of perpendicular magnetization at room temperature without magnetic fields, and the power consumption is 67 times smaller than that of the Pt control case. The high out-of-plane spin Hall conductivity is attributed to the conversion from in-plane spin to out-of-plane spin, induced by the crystal asymmetry of WTe2. Our work establishes a low-power perpendicular magnetization manipulation based on wafer-scale two-dimensional van der Waals heterostructures.

Combination therapy of niclosamide with gemcitabine inhibited cell proliferation and apoptosis via Wnt/ß-catenin/c-Myc signaling pathway by inducing ß-catenin ubiquitination in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with high morbidity and mortality rates worldwide. Owing to a lack of therapeutic options, the overall survival rate of patients with pancreatic cancer is low. Gemcitabine has been mainly used to treat patients with pancreatic cancer, but its efficacy is limited by chemoresistance. Therefore, a novel therapeutic agent for PDAC therapy is urgently needed. An anthelminthic drug, niclosamide, has already been researched in breast, lung, colon, and pancreatic cancer as an anti-cancer purpose by re-positioning its original purpose. However, combination therapy of gemcitabine and niclosamide was not informed yet. Here, we found that niclosamide co-administered with gemcitabine significantly inhibited tumorigenesis of pancreatic cancer compared to gemcitabine alone. Further, combining niclosamide and gemcitabine inhibited cell proliferation and induced apoptosis. Niclosamide induced cell cycle arrest at the G1 phase, and the levels of CDK4/6 and cyclin D1 were lowered after gemcitabine treatment. In addition, the combination of these chemical compounds more effectively increased the binding level of activated ß-catenin destruction complex and ß-catenin to enable phosphorylation, compared to gemcitabine alone. After phosphorylation, niclosamide - gemcitabine upregulated the ubiquitin level, which caused phosphorylated ß-catenin to undergo proteasomal degradation; the combination was more potent than gemcitabine alone. Finally, the combination more effectively suppressed tumor growth in vivo, compared to gemcitabine alone. Altogether, our results indicate that niclosamide synergistically enhances the antitumor effect of gemcitabine in pancreatic cancer, by inducing the degradation of ß-catenin with ubiquitination. Therefore, this drug combination can potentially be used in PDAC therapy.

Evaluating the Efficacy of Tension Band Wiring Fixation for Chaput Tubercle Fractures.

BACKGROUND: Chaput tubercle fractures, located at the attachment site of the anterior inferior tibiofibular ligament (AITFL) on the distal tibia, have the potential to destabilize the syndesmosis joint. This study aims to assess the effectiveness of tension band wiring (TBW) as a surgical intervention for managing Chaput fractures and the consequent syndesmosis instability. METHODS: A retrospective review of patient charts was undertaken for those who had undergone ankle fracture surgery from April 2019 through May 2022. The surgical procedure involved direct fixation of the Chaput fractures using the TBW method. Radiological assessments were performed using postoperative simple radiographs and computed tomography (CT) scans, while clinical outcomes were evaluated using the Olerud-Molander Ankle Score (OMAS) and the visual analog scale (VAS). RESULTS: The study included 21 patients. The average OMAS improved significantly, rising from 5.95 preoperatively to 83.57 postoperatively. Similarly, the average VAS score dropped from 7.95 before the surgery to 0.19 thereafter. Minor wound complications were reported by three patients, and one case of superficial infection was resolved with antibiotic therapy. CONCLUSIONS: Our findings suggest that the TBW technique is an effective surgical approach for treating Chaput fractures and associated syndesmosis instability. It provides reliable fixation strength and leads to improved long-term functional outcomes. Further research is needed to compare the TBW technique with alternative methods and optimize the treatment strategies for these complex ankle fractures.

Single or double Kirschner wire fixation: which provides better outcomes for pediatric proximal phalanx base fractures?

PURPOSE: The most common hand fracture in children is seen at the base of the proximal phalanx. This study aims to compare clinical outcomes of single versus double Kirschner wire pinning for pediatric proximal phalanx base fractures. PATIENTS AND METHODS: The retrospective study enrolled patients who underwent closed K-wire pinning for proximal phalanx base fractures from January 2016 to February 2022. We divided patients into two groups based on the number of K-wire inserted (single versus double). Demographics, removal of implant, complication rate were analyzed. Patients were asked to answer the Michigan Hand Outcomes Questionnaire (MHQ) by telephone. Data including fracture type, diaphyseal axis-metacarpal head angle (DHA) and Total Active Flexion Scale (TAFS) were analyzed. RESULTS: This study included 37 pediatric patients with proximal phalanx base fractures, treated with either single (n = 10) or double K-wire (n = 27) fixation. The mean operation time was significantly shorter for the single K-wire group. No significant differences were observed in complication rates, TAFS, implant removal times, MHQ, or pre- and post-operative DHA between the two groups. CONCLUSION: The single K-wire technique demonstrates similar effectiveness to the double K-wire technique in treating pediatric proximal phalanx base fractures, with the added benefit of shorter operation time. Therefore, the choice between using one or two K-wires should be determined based on the surgeon's proficiency and preference.

Spin current driven by ultrafast magnetization of FeRh.

Laser-induced ultrafast demagnetization is an important phenomenon that probes arguably the ultimate limits of the angular momentum dynamics in solid. Unfortunately, many aspects of the dynamics remain unclear except that the demagnetization transfers the angular momentum eventually to the lattice. In particular, the role and origin of electron-carried spin currents in the demagnetization process are debated. Here we experimentally probe the spin current in the opposite phenomenon, i.e., laser-induced ultrafast magnetization of FeRh, where the laser pump pulse initiates the angular momentum build-up rather than its dissipation. Using the time-resolved magneto-optical Kerr effect, we directly measure the ultrafast-magnetization-driven spin current in a FeRh/Cu heterostructure. A strong correlation between the spin current and the magnetization dynamics of FeRh is found even though the spin filter effect is negligible in this opposite process. This result implies that the angular momentum build-up is achieved by an angular momentum transfer from the electron bath (supplier) to the magnon bath (receiver) and followed by the spatial transport of angular momentum (spin current) and dissipation of angular momentum to the phonon bath (spin relaxation).