Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models.

One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently down-regulated the cell surface expression of the antigen-presenting molecule, CD1d, to suppress the function of iNKT cells. E protein is a small membrane protein and a viroporin that plays important roles in virion packaging and envelopment during viral morphogenesis. We showed that the transmembrane domain of E protein was responsible for suppressing CD1d expression by specifically reducing the level of mature, post-ER forms of CD1d, suggesting that it suppressed the trafficking of CD1d proteins and led to their degradation. Point mutations demonstrated that the putative ion channel function was required for suppression of CD1d expression and inhibition of the ion channel function using small chemicals rescued the CD1d expression. Importantly, we discovered that among seven human coronaviruses, only E proteins from highly pathogenic coronaviruses including SARS-CoV-2, SARS-CoV and MERS suppressed CD1d expression, whereas the E proteins of human common cold coronaviruses, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1, did not. These results suggested that E protein-mediated evasion of NKT cell function was likely an important pathogenesis factor, enhancing the virulence of these highly pathogenic coronaviruses. Remarkably, activation of iNKT cells with their glycolipid ligands, both prophylactically and therapeutically, overcame the putative viral immune evasion, significantly mitigated viral pathogenesis and improved host survival in mice. Our results suggested a novel NKT cell-based anti-SARS-CoV-2 therapeutic approach.

Dissecting the genetic basis of heterosis in elite super-hybrid rice.

Y900 is one of the top hybrid rice (Oryza sativa) varieties, with its yield exceeding 15 t·hm-2. To dissect the mechanism of heterosis, we sequenced the male parent line R900 and female parent line Y58S using long-read and Hi-C technology. High-quality reference genomes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 single-nucleotide polymorphisms, 299,149 insertions/deletions, and 4,757 structural variations. The level of variation between Y58S and R900 was the lowest among the comparisons of Y58S with other rice genomes. More than 75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the portion of Geng/japonica (GJ)-type genetic components from different male parents increased with yield increasing in their corresponding hybrids. Transcriptome analysis revealed that the partial dominance effect was the main genetic effect that constituted the heterosis of Y900. In the hybrid, both alleles from the two parents were expressed, and their expression patterns were dynamically regulated in different tissues. The cis-regulation was dominant for young panicle tissues, while trans-regulation was more common in leaf tissues. Overdominance was surprisingly prevalent in stems and more likely regulated by the trans-regulation mechanism. Additionally, R900 contained many excellent GJ haplotypes, such as NARROW LEAF1, Oryza sativa SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13, and Grain number, plant height, and heading date8, making it a good complement to Y58S. The fine-tuned mechanism of heterosis involves genome-wide variation, GJ introgression, key functional genes, and dynamic gene/allele expression and regulation pattern changes in different tissues and growth stages.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

Automatic detection of epilepsy from EEGs using a temporal convolutional network with a self-attention layer.

BACKGROUND: Over 60% of epilepsy patients globally are children, whose early diagnosis and treatment are critical for their development and can substantially reduce the disease's burden on both families and society. Numerous algorithms for automated epilepsy detection from EEGs have been proposed. Yet, the occurrence of epileptic seizures during an EEG exam cannot always be guaranteed in clinical practice. Models that exclusively use seizure EEGs for detection risk artificially enhanced performance metrics. Therefore, there is a pressing need for a universally applicable model that can perform automatic epilepsy detection in a variety of complex real-world scenarios. METHOD: To address this problem, we have devised a novel technique employing a temporal convolutional neural network with self-attention (TCN-SA). Our model comprises two primary components: a TCN for extracting time-variant features from EEG signals, followed by a self-attention (SA) layer that assigns importance to these features. By focusing on key features, our model achieves heightened classification accuracy for epilepsy detection. RESULTS: The efficacy of our model was validated on a pediatric epilepsy dataset we collected and on the Bonn dataset, attaining accuracies of 95.50% on our dataset, and 97.37% (A v. E), and 93.50% (B vs E), respectively. When compared with other deep learning architectures (temporal convolutional neural network, self-attention network, and standardized convolutional neural network) using the same datasets, our TCN-SA model demonstrated superior performance in the automated detection of epilepsy. CONCLUSION: The proven effectiveness of the TCN-SA approach substantiates its potential as a valuable tool for the automated detection of epilepsy, offering significant benefits in diverse and complex real-world clinical settings.

Diterpenoid Alkaloids from Delphinium liangshanense.

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.

Cell-free protein synthesis of CD1E and B2M protein and in vitro interaction.

CD1E, one of the most important glycolipid antigens on T cell membranes, is required for glycolipid antigen presentation on the cell surface. Cell-based recombinant expression systems have many limitations for synthesizing transmembrane proteins such as CD1E, including low protein yields and miss folding. To overcome these challenges, here we successfully synthesized high-quality soluble CD1E using an E.coli cell-free protein synthesis system (CFPS) with the aid of detergent. Following purification by Ni2+ affinity chromatography, we were able to obtain CD1E with ≥90% purity. Furthermore, we used the string website to predict the protein interaction network of CD1E and identified a potential binding partner━B2M. Similarly, we synthesized soluble B2M in the E.coli CFPS. Finally, we verified the interaction between CD1E and B2M by using Surface Plasmon Resonance (SPR). Taken together, the methods described here provide an alternative way to obtain active transmembrane protein and may facilitate future structural and functional studies on CD1E.

Circular RNA circ-AGFG1 contributes to esophageal squamous cell carcinoma progression and glutamine catabolism by targeting microRNA-497-5p/solute carrier family 1 member 5 axis.

Circular RNAs (circRNAs) have been shown to play important regulatory roles in human malignancies. However, the role of circRNA ArfGAP with FG repeats 1 (circ-AGFG1) in esophageal squamous cell carcinoma (ESCC) progression and its associated mechanism are still largely undefined. Cell proliferation was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was assessed by flow cytometry analysis. Transwell assay and wound healing assay were used to analyze cell invasion and migration abilities. The uptake of glutamine and the production of α-ketoglutarate and glutamate were analyzed using Glutamine Determination Kit, α-ketoglutarate Assay Kit and Glutamate Determination Kit. A xenograft tumor model was used to analyze the biological role of circ-AGFG1 in vivo . The interaction between microRNA-497-5p (miR-497-5p) and circ-AGFG1 or solute carrier family 1 member 5 (SLC1A5) was verified by dual-luciferase reporter assay. Circ-AGFG1 expression was upregulated in ESCC tissues and cell lines. Circ-AGFG1 silencing suppressed the proliferation, migration, invasion and glutaminolysis and triggered the apoptosis of ESCC cells. Circ-AGFG1 knockdown significantly slowed down tumor growth in vivo . Circ-AGFG1 acted as a sponge for miR-497-5p, and miR-497-5p interacted with the 3' untranslated region (3'UTR) of SLC1A5. miR-497-5p silencing largely abolished circ-AGFG1 silencing-induced effects in ESCC cells. miR-497-5p overexpression-mediated influences in ESCC cells were largely reversed by the addition of SLC1A5 expressing plasmid. Circ-AGFG1 could upregulate SLC1A5 expression by sponging miR-497-5p. In summary, circ-AGFG1 acted as an oncogene to elevate the malignant potential and promote the glutamine catabolism of ESCC cells by targeting the miR-497-5p/SLC1A5 axis.

Inhibition of Wnt7b reduces the proliferation, invasion, and migration of colorectal cancer cells.

OBJECTIVE: Colorectal cancer is one of the most common gastrointestinal tumors. The role of Wnt7b as a ligand of the Wnt signaling pathway in colorectal cancer remains to be studied. Through bioinformatics online analysis, we found that Wnt7b is abnormally highly expressed in a variety of gastrointestinal tumors. This study mainly explored the effects of Wnt7b regulating the Wnt/ß-catenin signaling pathway on the proliferation, migration, and invasion of SW480 cells in colorectal cancer. METHODS AND RESULTS: Applying the TCGA data set, Wnt7b was found to be highly expressed in most gastrointestinal tumor samples. Real-time quantitative PCR(q-PCR), Western blotting(WB) results showed that Wnt7b was significantly higher expressed in colorectal cancer cell lines compared with normal intestinal epithelial cells. SW480 cells transfected with the sh-Wnt7b showed successful knockdown of Wnt7b. MTT colorimetry showed the proliferation ability of sh-Wnt7b group decreased significantly compared with the non-transfected group. The results of double staining flow cytometry showed that the sh-Wnt7b group had more apoptosis. Cell scratch test showed that the cell migration rate of sh-wnt7b group considerably reduced. The Transwell invasion experiment demonstrated that the number of cell invasions in the sh-Wnt7b group decreased significantly. After SW480 cells was transfected with sh-Wnt7b, the protein levels of ß-catenin, CCND1, and CD44 in this group of cells were detected to be reduced by WB, and the same results were obtained by q-PCR detection of mRNA. CONCLUSION: Wnt7b is highly expressed in colorectal cancer cells, which may affect the proliferation, migration, and invasion of colorectal cancer cells by activating the Wnt/ß-catenin signaling pathway.

LZerD webserver for pairwise and multiple protein-protein docking.

Protein complexes are involved in many important processes in living cells. To understand the mechanisms of these processes, it is necessary to solve the 3D structures of the protein complexes. When protein complex structures have not yet been determined by experiment, protein-protein docking tools can be used to computationally model the structures of these complexes. Here, we present a webserver which provides access to LZerD and Multi-LZerD protein docking tools. The protocol provided by the server have performed consistently among the top in the CAPRI blind evaluation. LZerD docks pairs of structures, while Multi-LZerD can dock three or more structures simultaneously. LZerD uses a soft protein surface representation with 3D Zernike descriptors and explores the binding pose space using geometric hashing. Multi-LZerD performs multi-chain docking by combining pairwise solutions by LZerD. Both methods output full-atom docked models of the input proteins. Users can also input distance constraints between interacting or non-interacting residues as well as residues that locate at the interface or far from the interface. The webserver is equipped with a user-friendly panel that visualizes the distribution and structures of binding poses of top scoring models. The LZerD webserver is available at https://lzerd.kiharalab.org.

Interspecific differences in thermal tolerance landscape explain aphid community abundance under climate change.

A single critical thermal limit is often used to explain and infer the impact of climate change on geographic range and population abundance. However, it has limited application in describing the temporal dynamic and cumulative impacts of extreme temperatures. Here, we used a thermal tolerance landscape approach to address the impacts of extreme thermal events on the survival of co-existing aphid species (Metopolophium dirhodum, Sitobion avenae and Rhopalosiphum padi). Specifically, we built the thermal death time (TDT) models based on detailed survival datasets of three aphid species with three ages across a broad range of stressful high (34-40 °C) and low (-3∼-11 °C) temperatures to compare the interspecific and developmental stage variations in thermal tolerance. Using these TDT parameters, we performed a thermal risk assessment by calculating the potential daily thermal injury accumulation associated with the regional temperature variations in three wheat-growing sites along a latitude gradient. Results showed that M. dirhodum was the most vulnerable to heat but more tolerant to low temperatures than R. padi and S. avenae. R. padi survived better at high temperatures than Sitobion avenae and M. dirhodum but was sensitive to cold. R. padi was estimated to accumulate higher cold injury than the other two species during winter, while M. dirhodum accrued more heat injury during summer. The warmer site had higher risks of heat injury and the cooler site had higher risks of cold injury along a latitude gradient. These results support recent field observations that the proportion of R. padi increases with the increased frequency of heat waves. We also found that young nymphs generally had a lower thermal tolerance than old nymphs or adults. Our results provide a useful dataset and method for modelling and predicting the consequence of climate change on the population dynamics and community structure of small insects.

Study on the Relationship Between Diet, Physical Health and Gut Microflora of Chinese College Students.

Many elements of a modern lifestyle influence the gut microbiota but few studies have explored the effect of physical health level. This study was aimed to explore the relationship between diet, physical health and gut microbiota in Chinese college students. A total of 69 college students were recruited, including 27 college athletes (AS group) and 42 healthy controls (HC group). Fecal samples were collected for 16S rRNA sequencing. According to National Standards for Students' Physical Health (2014 revision), physical fitness measurements, dietary intake and health-related data were collected via questionnaires. ①According to the physical fitness scores, the physical fitness level of AS group was significantly higher than that of HC group (P < 0.05), there were no significant differences between the two groups in the frequency of intake of food. The frequency and duration of physical activity in the AS group were higher than those in the HC group (P < 0.05); ②The proportion and relative abundances of microorganism composition is varying at two groups: on the phylum level, AS group had mainly increased Firmicutes, Actinobacteria and reduced Bacteroidetes, Proteobacteria; on the genus level, AS group had mainly increased Faecalibacterium, Bifidobacterium and reduced Bacteroides; ③The associations with the 10 most abundant bacterial genera and physical fitness, dietary factors were investigated. Changes in the gut microbiota abundance can be sometimes reflective of a physical health status. Loss of the balance of gut microbial populations will lead to flora disorders and diseases. Therefore, further studies are needed to reveal the mechanisms behind the gut microbiota in its potential role.

Feature Extraction of the Brain's Dynamic Complex Network Based on EEG and a Framework for Discrimination of Pediatric Epilepsy.

Most of the current complex network studies about epilepsy used the electroencephalogram (EEG) to directly construct the static complex network for analysis and discarded the dynamic characteristics. This study constructed the dynamic complex network on EEG from pediatric epilepsy and pediatric control when they were asleep by the sliding window method. Dynamic features were extracted and incorporated into various machine learning classifiers to explore their classification performances. We compared these performances between the static and dynamic complex network. In the univariate analysis, the initially insignificant topological characteristics in the static complex network can be transformed to be significant in the dynamic complex network. Under most connectivity calculation methods between leads, the accuracy of using dynamic complex network features for discrimination was higher than that of static complex network features. Particularly in the imaginary part of the coherency function (iCOH) method under the full-frequency band, the discrimination accuracies of most machine learning classifiers were higher than 95%, and the discrimination accuracies in the higher-frequency band (beta-frequency band) and the full-frequency band were higher than that of the lower-frequency bands. Our proposed method and framework could efficiently summarize more time-varying features in the EEG and improve the accuracies of the discrimination of the machine learning classifiers more than using static complex network features.

A global map of the protein shape universe.

Proteins are involved in almost all functions in a living cell, and functions of proteins are realized by their tertiary structures. Obtaining a global perspective of the variety and distribution of protein structures lays a foundation for our understanding of the building principle of protein structures. In light of the rapid accumulation of low-resolution structure data from electron tomography and cryo-electron microscopy, here we map and classify three-dimensional (3D) surface shapes of proteins into a similarity space. Surface shapes of proteins were represented with 3D Zernike descriptors, mathematical moment-based invariants, which have previously been demonstrated effective for biomolecular structure similarity search. In addition to single chains of proteins, we have also analyzed the shape space occupied by protein complexes. From the mapping, we have obtained various new insights into the relationship between shapes, main-chain folds, and complex formation. The unique view obtained from shape mapping opens up new ways to understand design principles, functions, and evolution of proteins.

Effects of SARS-CoV-2 and its functional receptor ACE2 on the cardiovascular system.

The clinical manifestations of COVID-19 are mainly respiratory symptoms, but some patients present with cardiovascular system disease such as palpitations and shortness of breath as the first or secondary symptoms. In this paper, we describe the characteristics of SARS-CoV­2 and its functional receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, we explore the impact of virus-induced myocardial damage, decreased ACE2 activity, immune imbalance, hypoxemia, and heart damage caused by antiviral drugs.

Automatic Changes Detection between Outdated Building Maps and New VHR Images Based on Pre-Trained Fully Convolutional Feature Maps.

Detecting changes between the existing building basemaps and newly acquired high spatial resolution remotely sensed (HRS) images is a time-consuming task. This is mainly because of the data labeling and poor performance of hand-crafted features. In this paper, for efficient feature extraction, we propose a fully convolutional feature extractor that is reconstructed from the deep convolutional neural network (DCNN) and pre-trained on the Pascal VOC dataset. Our proposed method extract pixel-wise features, and choose salient features based on a random forest (RF) algorithm using the existing basemaps. A data cleaning method through cross-validation and label-uncertainty estimation is also proposed to select potential correct labels and use them for training an RF classifier to extract the building from new HRS images. The pixel-wise initial classification results are refined based on a superpixel-based graph cuts algorithm and compared to the existing building basemaps to obtain the change map. Experiments with two simulated and three real datasets confirm the effectiveness of our proposed method and indicate high accuracy and low false alarm rate.

Herpes Simplex Virus 1 Specifically Targets Human CD1d Antigen Presentation To Enhance Its Pathogenicity.

Herpes simplex virus 1 (HSV-1) is one of the most prevalent herpesviruses in humans and represents a constant health threat to aged and immunocompromised populations. How HSV-1 interacts with the host immune system to efficiently establish infection and latency is only partially known. CD1d-restricted NKT cells are a critical arm of the host innate immune system and play potent roles in anti-infection and antitumor immune responses. We discovered previously that upon infection, HSV-1 rapidly and efficiently downregulates CD1d expression on the cell surface and suppresses the function of NKT cells. Furthermore, we identified the viral serine/threonine protein kinase US3 as a major viral factor downregulating CD1d during infection. Interestingly, neither HSV-1 nor its US3 protein efficiently inhibits mouse CD1d expression, suggesting that HSV-1 has coevolved with the human immune system to specifically suppress human CD1d (hCD1d) and NKT cell function for its pathogenesis. This is consistent with the fact that wild-type mice are mostly resistant to HSV-1 infection. On the other hand, in vivo infection of CD1d-humanized mice (hCD1d knock-in mice) showed that HSV-1 can indeed evade hCD1d function and establish infection in these mice. We also report here that US3-deficient viruses cannot efficiently infect hCD1d knock-in mice but infect mice lacking all NKT cells at a higher efficiency. Together, these studies supported HSV-1 evasion of human CD1d and NKT cell function as an important pathogenic factor for the virus. Our results also validated the potent roles of NKT cells in antiherpesvirus immune responses and pointed to the potential of NKT cell ligands as adjuvants for future vaccine development.IMPORTANCE Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We reported previously that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule, CD1d, so as to evade the antiviral function of NKT cells. Here we demonstrated that the virus has coevolved with the human CD1d and NKT cell system and that NKT cells indeed play potent roles in anti-HSV immune responses. These studies point to the great potential of exploring NKT cell ligands as adjuvants for HSV vaccines.

TGF-ß1 and connexin-43 expression in neurogenic bladder from rats with sacral spinal cord injury.

AIMS: Sacral spinal cord injury (SCI) could induce underactive bladder (UAB). Malfunction of connexin 43 (CX43) regulated by TGF-ß1 might involve in urinary bladder dysfunction. We studied the changes of CX43 and TGF-ß1/Smad3 signaling in detrusor of neurogenic bladder (NB) in sacral SCI rats. METHODS: Sacral SCI was produced by hemisection (SSCH) or transection (SSCT) of spinal cord between L4 and L5 in female Wistar rats. BBB scores, residual urine volume and bladder weight as well as characteristic cystometric parameters at 6th week were used to confirm the successful establishment of NB. Western blotting and qRT-PCR were used to exam the protein and mRNA expression levels of CX43, CX45, TGF-ß1, and Smad3 in detrusor. RESULTS: BBB scores were significantly decreased, with the lowest in SSCT rats (P < 0.01). The residual urine volume, mean bladder weight, and cystometric parameters were increased, with the highest in SSCT rats. CX43 and phospho-CX43 protein levels were significantly decreased, but those of TGF-ß1, Smad3, and phospho-Smad3 were significantly increased. It was the protein and mRNA levels of CX43 but not those of CX45 which were decreased in negative accordance with those of TGF-ß1 and Smad3. Those changes were more significant in SSCT than in SSCH rats. CONCLUSIONS: This study indicates that voiding dysfunction is related to the decreased CX43 function in detrusor from NB. TGF-ß1/Smad3 signaling might be involved in the down-regulation of CX43 in SCI rats. Early regulation of CX43 might be beneficial to patients with voiding dysfunction.

Wuzhi Tablet (Schisandra sphenanthera Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study.

Tacrolimus is a potent but expensive first-line immunosuppressant, thus solutions to reduce tacrolimus consumption while maintain therapeutic level are in urgent need. A two-phase prospective study was conducted to assess the efficacy of an ethanolic extraction preparation of Schisandra sphenanthera (Wuzhi tablet) as a tacrolimus-sparing agent in renal transplant recipients who were high-dose tacrolimus consumers (CYP3A5*1 allele carriers, CYP3A5 expressers). A total of 12 patients were included in the Part I study. After co-administration of Wuzhi tablet, the average individual increment (%) in dose-adjusted C0, Cmax and AUC0-12 hour of tacrolimus were 198.8% (95% CI 149.2, 248.3), 111.0% (95% CI 63.4, 158.6) and 126.1% (95% CI 89.4, 162.8), respectively (P < 0.01), while the average individual reduction (%) in tacrolimus daily dose was 40.9% (95% CI 25.2, 56.6) (P < 0.01). Subsequently, 32 patients were enrolled in a prospective, randomized, controlled study and randomly assigned to receive tacrolimus by CYP3A5 genotype plus Wuzhi tablet co-administration guided dosing (study group) or standard dosing (control group). Besides less tacrolimus dose requirement (P < 0.01), a more accurate tacrolimus initial dose characterized by lower incidence of out-of-range C0 after initial dose (P < 0.01) and fewer dose changes (P < 0.01) was found in the study group. Moreover, no significant differences in acute rejection rate and serum creatinine levels were observed between two groups. Our results show that CYP3A5 genotype plus Wuzhi tablet co-administration guided tacrolimus dosing is a promising therapy for CYP3A5 expressers in the early post-transplant stage, while further study with a larger sample size is required to prove these findings.

[Conjunctival Fas-FasL expression in chronic Stevens-Johnson syndrome].

OBJECTIVE: To investigate the expression level of Fas-FasL in conjunctiva tissue of chronic Stevens-Johnson syndrome (SJS) patients and to analyze the role of Fas-FasL pathway in the mechanism of ocular damage related to SJS. METHODS: Conjunctiva tissue was obtained during symblepharon release operation and cryostat sectioned at 5 µm. The tissue morphology was observed by electron microscopy. The expression of Fas-FasL (CD95/CD178) in conjunctiva was detected by immunohistochemistry (direct immunofluorescence). The conjunctiva tissue of normal people was also observed and tested as contrast group. RESULTS: The pathogenic changes included incrassation of epithelium and cavity of mucous glands in the sub-epithelium. The expression of Fas in SJS patients focusing in the basal layer of epithelium appeared a lower level compared to that in normal human conjunctiva, which distributed equally in all layers of epithelium. The expressions of FasL in SJS patients and normal people were both weak. CONCLUSIONS: The low level expression of Fas-FasL in conjunctiva of SJS patients has certain effect on the chronic ocular damage.