Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation.

BACKGROUND: Liver transplantation is treatment option for patients with end stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT). METHODS: We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately prior to LDLT, and renal function status was followed up for 3 consecutive days postoperatively. RESULTS: Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early post-transplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT. CONCLUSION: AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AK.

Factors influencing health-related quality of life in women with endometriosis: A cross-sectional study.

This study aimed to assess the health-related quality of life and identify its associated factors in women with endometriosis. A cross-sectional correlation study design and convenience sampling were conducted in the gynecological outpatient clinic of a teaching hospital in northern Taiwan. A total of 216 women with endometriosis were recruited. The data were collected using structured questionnaires and analyzed using descriptive and inferential statistics. Participants reported a moderate level of health-related quality of life. The most significant impact of endometriosis on health-related quality of life was emotional well-being, followed by feeling of control or powerless, pain, social support, and self-image. Educational attainment, menstrual cycle, period length, perceived menstrual flow, symptom distress, and self-management strategies explained 66% of the variance in health-related quality of life. Factors influencing health-related quality of life in women with endometriosis play a key role in promoting women's well-being. Interventions based on these related factors should be developed and taken into practice to effectively manage the disease-related symptoms for women with endometriosis and thereby improve their overall health-related quality of life.

Hair Follicle Transit-Amplifying Cells Phagocytose Dead Cells after Radiotherapeutic and Chemotherapeutic Injuries for Timely Regeneration.

Efficient clearance of dead cells is critical for tissue regeneration after injuries. How dead cells are removed from the skin after radiotherapy and chemotherapy is unclear. In this study, we found that radiotherapeutic and chemotherapeutic damage induced extensive apoptosis of highly proliferative transit-amplifying cells in hair follicles. These apoptotic cells disappeared rapidly in the early stage of regenerative attempts, and the lost structures were regenerated with transient and low-level inflammation. Without the recruitment of macrophages as scavengers, the dying cells were engulfed directly by adjacent surviving transit-amplifying cells, which produced mature phagosomes through fusion with lysosomes in a manner similar to professional phagocytosis and remained active in proliferation. Autophagy did not contribute significantly to the clearance of engulfed cell debris. Perturbing phagocytosis in the transit-amplifying cells hindered apoptotic cell removal, delayed structural recovery, and aggravated hair loss. Therefore, transit-amplifying cells are capacitated with both proliferative and efferocytic functions that facilitate tissue regeneration after tissue injury.

Delayed Collagen Production without Myofibroblast Formation Contributes to Reduced Scarring in Adult Skin Microwounds.

In adult mammals, wound healing predominantly follows a fibrotic pathway, culminating in scar formation. However, cutaneous microwounds generated through fractional photothermolysis, a modality that produces a constellation of microthermal zones, exhibit a markedly different healing trajectory. Our study delineates the cellular attributes of these microthermal zones, underscoring a temporally limited, subclinical inflammatory milieu concomitant with rapid re-epithelialization within 24 hours. This wound closure is facilitated by the activation of genes associated with keratinocyte migration and differentiation. In contrast to macrothermal wounds, which predominantly heal through a robust myofibroblast-mediated collagen deposition, microthermal zones are characterized by absence of wound contraction and feature delayed collagen remodeling, initiating 5-6 weeks after injury. This distinct wound healing is characterized by a rapid re-epithelialization process and a muted inflammatory response, which collectively serve to mitigate excessive myofibroblast activation. Furthermore, we identify an initial reparative phase characterized by a heterogeneous extracellular matrix protein composition, which precedes the delayed collagen remodeling. These findings extend our understanding of cutaneous wound healing and may have significant implications for the optimization of therapeutic strategies aimed at mitigating scar formation.

The cellular responses of corneal fibroblasts to cyclic stretching loads.

Mechanical signaling plays a crucial role in maintaining extracellular matrix (ECM) homeostasis in various structures. In this study, we investigated the responses of corneal fibroblasts to cyclic stretching loads using an in vitro cell culture system. Bovine corneal fibroblasts were cultured and subjected to equibiaxial cyclic strain of 15% for 72 h at a frequency of 0.25 Hz, with bovine skin fibroblasts used as a comparison. We explored various cellular behaviors, including morphological changes, cell proliferation, and metabolism in response to mechanical stretching loads. The expression of genes, protein secretion, and enzymatic activity for several major metalloproteinases was also determined through Q-PCR, Western blot, and gel zymography. Additionally, we investigated the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in the corneal fibroblasts when subjected to mechanical stimuli. Our findings revealed that, compared to skin fibroblasts, corneal fibroblasts were reluctant to morphological changes in response to a prolonged (72 h) and high-amplitude (15% of strain) cyclic stretching load. However, cyclic stretching loads stimulated the upregulation of MMP-2 expression in corneal fibroblasts via the MAPK signaling pathways involving extracellular signal-regulated kinase and p38. Together with a lack of upregulation in type I collagen expression, our results indicate the induction of the ECM degradation process in corneal fibroblasts in response to cyclic stretching. These findings emphasize the mechanoresponsive nature of corneal fibroblasts and shed light on the potential impact of intense mechanical stress on the cornea in both normal and pathological conditions such as keratoconus, providing valuable insights for understanding corneal mechanobiology.

Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Complex Cell-Cell Communication Networks in the Mouse Cornea.

Purpose: To generate a single-cell RNA-sequencing (scRNA-seq) map and construct cell-cell communication networks of mouse corneas. Methods: C57BL/6 mouse corneas were dissociated to single cells and subjected to scRNA-seq. Cell populations were clustered and annotated for bioinformatic analysis using the R package "Seurat." Differential expression patterns were validated and spatially mapped with whole-mount immunofluorescence staining. Global intercellular signaling networks were constructed using CellChat. Results: Unbiased clustering of scRNA-seq transcriptomes of 14,732 cells from 40 corneas revealed 17 cell clusters of six major cell types: nine epithelial cell, three keratocyte, two corneal endothelial cell, and one each of immune cell, vascular endothelial cell, and fibroblast clusters. The nine epithelial cell subtypes included quiescent limbal stem cells, transit-amplifying cells, and differentiated cells from corneas and two minor conjunctival epithelial clusters. CellChat analysis provided an atlas of the complex intercellular signaling communications among all cell types. Conclusions: We constructed a complete single-cell transcriptomic map and the complex signaling cross-talk among all cell types of the cornea, which can be used as a foundation atlas for further research on the cornea. This study also deepens the understanding of the cellular heterogeneity and heterotypic cell-cell interaction within corneas.

SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer.

Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

Valley Polarized Holes Induced Exciton Polaron Valley Splitting.

Monolayer transition metal dichalcogenide semiconductors are promising valleytronic materials. Among various quasi-particle excitations hosted by the system, the valley polarized holes are particularly interesting due to their long valley lifetime preserved by the large spin-orbit splitting and spin-valley locking in the valence band. Here we report that in the absence of any magnetic field a surprising valley splitting of exciton polarons can be induced by such valley polarized holes in monolayer WSe2. The size of the splitting is comparable to that of the Zeeman effect in a magnetic field as high as 7 T and offers a quantitative approach to extract the hole density imbalance between the two valleys. We find that the density difference can easily achieve more than 1011 per cm2, and it is tunable by gate voltage as well as optical excitation power. Our study highlights the response of exciton polarons to optical pumping and advances understanding of valley dependent phenomena in monolayer transition metal dichalcogenide.

Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism.

Phenotypic heterogeneity is very common in genetic systems and in human diseases and has important consequences for disease diagnosis and treatment. In addition to the many genetic and non-genetic (e.g., epigenetic, environmental) factors reported to account for part of the heterogeneity, we stress the importance of stochastic fluctuation and regulatory network topology in contributing to phenotypic heterogeneity. We argue that a threshold effect is a unifying principle to explain the phenomenon; that ultrasensitivity is the molecular mechanism for this threshold effect; and discuss the three conditions for phenotypic heterogeneity to occur. We suggest that threshold effects occur not only at the cellular level, but also at the organ level. We stress the importance of context-dependence and its relationship to pleiotropy and edgetic mutations. Based on this model, we provide practical strategies to study human genetic diseases. By understanding the network mechanism for ultrasensitivity and identifying the critical factor, we may manipulate the weak spot to gently nudge the system from an ultrasensitive state to a stable non-disease state. Our analysis provides a new insight into the prevention and treatment of genetic diseases.

Percutaneous transhepatic duodenal drainage is good option for afferent loop syndrome for obstructive colorectal cancer patient with history of Billroth's operation II: A case report of a rare postoperative complication.

Key Clinical Message: Temporal percutaneous transhepatic duodenum drainage (PTDD) seems to be effective in the treatment of postoperative afferent loop syndrome (ALS) following transverse loop colostomy for obstructive colorectal cancer. Abstract: Management of obstructive colorectal cancer still remains a challenge. There are various options with different risks of mortality and mobility for obstructive colorectal cancer. A rare unexpected postoperative ALS following a low anterior resection and transverse loop colostomy for obstructive colorectal cancer is presented in this report. A 64-year-old man had the acute ALS had been noted 10 days after transverse loop colostomy. An option was temporal PTDD treatment in the patient with history of Billroth's operation II for upper gastrointestinal bleeding 30 years ago. Acute ALS was treated by temporal PTDD. The drainage tube for PTDD was not removed until closure of the transverse colostomy 2 months later. The patient recovered uneventfully. Acute ALS after transverse loop colostomy for obstructive colorectal cancer is rare and has never been reported in the literature. The mechanism of acute ALS after construction of a loop colostomy and the treatment strategy of PTDD for acute ALS is presented.

A salivary GMC oxidoreductase of Manduca sexta re-arranges the green leaf volatile profile of its host plant.

Green leaf volatiles (GLVs) are short-chain oxylipins that are emitted from plants in response to stress. Previous studies have shown that oral secretions (OS) of the tobacco hornworm Manduca sexta, introduced into plant wounds during feeding, catalyze the re-arrangement of GLVs from Z-3- to E-2-isomers. This change in the volatile signal however is bittersweet for the insect as it can be used by their natural enemies, as a prey location cue. Here we show that (3Z):(2E)-hexenal isomerase (Hi-1) in M. sexta's OS catalyzes the conversion of the GLV Z-3-hexenal to E-2-hexenal. Hi-1 mutants that were raised on a GLV-free diet showed developmental disorders, indicating that Hi-1 also metabolizes other substrates important for the insect's development. Phylogenetic analysis placed Hi-1 within the GMCß-subfamily and showed that Hi-1 homologs from other lepidopterans could catalyze similar reactions. Our results indicate that Hi-1 not only modulates the plant's GLV-bouquet but also functions in insect development.

Identification of silk components in the bombycoid moth Andraca theae (Endromidae) reveals three fibroin subunits resembling those of Bombycidae and Sphingidae.

The silk produced by Lepidoptera caterpillars is a mixture of proteins secreted by the transformed labial glands, the silk glands (SG). The silk fiber consists of insoluble filamentous proteins that form a silk core and are produced in the posterior part of the SG and soluble coat proteins consisting of sericins and various other polypeptides secreted in the middle part of the SG. We constructed a silk gland specific transcriptome of Andraca theae and created a protein database required for peptide mass fingerprinting. We identified major silk components by proteomic analysis of cocoon silk and by searching for homologies with known silk protein sequences from other species. We identified 30 proteins including a heavy chain fibroin, a light chain fibroin and fibrohexamerin (P25) that form the silk core, as well as members of several structural families that form the silk coating. To uncover the evolutionary relationships among silk proteins, we included orthologs of silk genes from several recent genome projects and performed phylogenetic analyses. Our results confirm the recent molecular classification that the family Endromidae appears to be slightly more distant from the family Bombycidae. Our study provides important information on the evolution of silk proteins in the Bombycoidea, which is needed for proper annotation of the proteins and future functional studies.

Honey bee foraging ability suppressed by imidacloprid can be ameliorated by adding adenosine.

Honey bees are important pollinators in most ecosystem, but they are currently facing many threats, which have led to a reduction in their population. Previous studies have indicated that neonicotinoid pesticide can impair the memory and learning ability of honey bees, which can eventually lead to a decline in their foraging and homing abilities. In this study, we investigated the homing ability barrier from the perspective of energy supply. We believe that when worker bees experience stress, their energy supply may shift from pro-movement to pro-resistance; this will lead to inadequate energy provision to the flight muscles, causing a reduction in wingbeat frequency and impairing the flight ability of the worker bees. To test this, the worker bees were treated with imidacloprid, and wing beats between the treatment groups were compared. Their glucose, glycogen, trehalose, and ATP contents were also measured, and their genes for energy metabolism and resistance were analyzed. The addition of adenosine improved the ATP content and helped recover the wingbeat frequency of the worker bees. The preliminary results obtained showed that wingbeat frequency and glucose content in the worker bees treated with imidacloprid were significantly lower than those in the control group. This result is consistent with our hypothesis and demonstrates that energy supply imbalances can prevent worker bees from returning to their hives.

Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations.

Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.

Elevated temperature affects energy metabolism and behavior of bumblebees.

Bumblebees (Bombus eximius) are one of the most prominent pollinators in the agricultural industry because of their adaptation to temperate climates and pollination behavior (buzz pollination). Several studies have explained the need to increase conservation efforts for bumblebees due to climate change, but studies on the impact of climate change on pollination behavior of bumblebees have been limited. The present study investigated the effect of elevated temperatures on the survival and physiology of bumblebees. The behavioral changes in flight ability and pollen collection were also determined. We found that elevated temperature affects the survival rate and appetite of bumblebees. Gene expression analysis suggested that the energy metabolic pathway tends to involve anaerobic respiration during heat stress. The energy produced is mainly used to maintain essential physiological functions, such as expression of heat shock proteins and conversion of peroxides to harmless molecules. Energy distributed to flight muscles is reduced during heat stress, resulting in lower wing beating frequency. In addition, the flight path of bumblebees is shortened during heat stress, thereby further contributing to reduced pollen collection. These results demonstrate that elevated temperatures cause detrimental effects to bumblebees and can also potentially reduce crop production.

Emergence and Persistent Dominance of SARS-CoV-2 Omicron BA.2.3.7 Variant, Taiwan.

Since April 2022, waves of SARS-CoV-2 Omicron variant cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we analyzed 2,405 PCR-positive swab samples from 2,339 persons and identified the Omicron BA.2.3.7 variant as a major lineage within recent community outbreaks in Taiwan.

Using Transfer Learning of Convolutional Neural Network on Neck Radiographs to Identify Acute Epiglottitis.

Acute epiglottitis (AE) is a life-threatening condition and needs to be recognized timely. Diagnosis of AE with a lateral neck radiograph yields poor reliability and sensitivity. Convolutional neural networks (CNN) are powerful tools to assist the analysis of medical images. This study aimed to develop an artificial intelligence model using CNN-based transfer learning to identify AE in lateral neck radiographs. All cases in this study are from two hospitals, a medical center, and a local teaching hospital in Taiwan. In this retrospective study, we collected 251 lateral neck radiographs of patients with AE and 936 individuals without AE. Neck radiographs obtained from patients without and with AE were used as the input for model transfer learning in a pre-trained CNN including Inception V3, Densenet201, Resnet101, VGG19, and Inception V2 to select the optimal model. We used five-fold cross-validation to estimate the performance of the selected model. The confusion matrix of the final model was analyzed. We found that Inception V3 yielded the best results as the optimal model among all pre-train models. Based on the average value of the fivefold cross-validation, the confusion metrics were obtained: accuracy = 0.92, precision = 0.94, recall = 0.90, and area under the curve (AUC) = 0.96. Using the Inception V3-based model can provide an excellent performance to identify AE based on radiographic images. We suggest using the CNN-based model which can offer a non-invasive, accurate, and fast diagnostic method for AE in the future.

Enhancing the insecticidal potential of a baculovirus by overexpressing the mammalian ß-galactosyl binding protein galectin-1.

BACKGROUND: Bio-pesticide development is an important area of research in agriculture, in which viruses are an essential tool. Infection by entomological pathogenic viruses kills agricultural pests, and viral progenies are disseminated to infect more pests, eventually achieving long-term pest control in the field. Of the current virus-based pest control models, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the most studied. AcMNPV belongs to the Baculoviridae family and can infect many lepidopterans. Although AcMNPV has been previously demonstrated to be a potential pest-control tool, its long virus infection cycle has made field applications challenging. To overcome this, we generated a recombinant baculovirus that can express mammalian galectin-1, which is a galactoside-binding protein that binds to the peritrophic matrix in the midgut of lepidopteran pests and induces perforation of the membrane. RESULTS: Hosts infected with a recombinant virus that expressed mammalian galectin-1 exhibited reduced appetite and died sooner in both laboratory and small-scale field studies, suggesting that the overexpression of galectin-1 can more efficiently eliminate pest hosts. In addition to disrupting the integrity of the peritrophic matrix, the immune system of hosts infected with recombinant baculovirus carrying the galectin-1 gene was suppressed, making hosts more vulnerable to secondary infection. CONCLUSION: Galectin-1 has been shown to affect immune responses in mammals, including humans, but to our knowledge, the effect of galectin-1 on insect immune systems had not been previously reported. Our results demonstrated that the pest-control potential of baculoviruses can be improved by using a recombinant baculovirus that overexpresses mammalian galectin-1 in hosts. © 2022 Society of Chemical Industry.

Axial Higgs mode detected by quantum pathway interference in RTe3.

The observation of the Higgs boson solidified the standard model of particle physics. However, explanations of anomalies (for example, dark matter) rely on further symmetry breaking, calling for an undiscovered axial Higgs mode1. The Higgs mode was also seen in magnetic, superconducting and charge density wave (CDW) systems2,3. Uncovering the vector properties of a low-energy mode is challenging, and requires going beyond typical spectroscopic or scattering techniques. Here we discover an axial Higgs mode in the CDW system RTe3 using the interference of quantum pathways. In RTe3 (R = La, Gd), the electronic ordering couples bands of equal or different angular momenta4-6. As such, the Raman scattering tensor associated with the Higgs mode contains both symmetric and antisymmetric components, which are excited via two distinct but degenerate pathways. This leads to constructive or destructive interference of these pathways, depending on the choice of the incident and Raman-scattered light polarization. The qualitative behaviour of the Raman spectra is well captured by an appropriate tight-binding model, including an axial Higgs mode. Elucidation of the antisymmetric component is direct evidence that the Higgs mode contains an axial vector representation (that is, a pseudo-angular momentum) and hints that the CDW is unconventional. Thus, we provide a means for measuring quantum properties of collective modes without resorting to extreme experimental conditions.

Observation of Ultrastrong Coupling between Substrate and the Magnetic Topological Insulator MnBi2Te4.

The intrinsic magnetic topological insulator MnBi2Te4 has attracted significant interest recently as a promising platform for exploring exotic quantum phenomena. Here we report that, when atomically thin MnBi2Te4 is deposited on a substrate such as silicon oxide or gold, there is a very strong mechanical coupling between the atomic layer and the supporting substrate. This is manifested as an intense low-frequency breathing Raman mode that is present even for monolayer MnBi2Te4. Interestingly, this coupling turns out to be stronger than the interlayer coupling between the MnBi2Te4 atomic layers. We further found that these low-energy breathing modes are highly sensitive to sample degradation, and they become drastically weaker upon ambient air exposure. This is in contrast to the higher energy optical phonon modes which are much more robust, suggesting that the low-energy Raman modes found here can be an effective indicator of sample quality.