H19 lncRNA triggers ferroptosis, exacerbating ox-LDL-induced artery endothelial cell damage in vitro.

BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

Optimization of Graft Position at the Tibia Footprint in Anterior Cruciate Ligament Revision-Lasso Technique.

In anterior cruciate ligament (ACL) revision cases, the resultant bigger aperture at the tibia footprint can cause graft instability. The increased movement hinders bone-graft integration and leads to graft abrasion. This article describes a technique to optimize graft stability when using a soft tissue graft for ACL revision. The technique is used when there is suspicion of size mismatch between the new tibia footprint aperture and the graft. The first stage involves passing a suture via an anterolateral tibial tunnel connecting with the revision tibia tunnel distal to the tibia footprint aperture. The new graft is subsequently deployed, and the potential discrepancy between graft diameter and aperture is confirmed. The second stage involves placing 2 pulling sutures on the new graft and passing them into the anterolateral tibial tunnel. The tensioned and anchored pulling sutures secure graft stability at the tibia footprint, and the graft distal to that is fixed routinely. The lasso technique stabilizes the new graft at the tibia footprint by tensioning it in a distal and anterolateral direction. For selected cases, this technique enables a 1-stage ACL revision with a soft tissue graft when faced with graft instability at the tibia footprint.

The potential of RNA therapeutics in dermatology.

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.

The influence of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life of patients with sarcopenia receiving haemodialysis: a randomised controlled trial.

OBJECTIVE: To study the effect of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life in patients with sarcopenia receiving maintenance haemodialysis (MHD). METHODS: Eligible patients with sarcopenia in our hospital were randomly assigned to a control group (n = 24) and an intervention group (n = 25). The control group received conventional dialysis treatment, while the intervention group underwent mindfulness meditation combined with progressive muscle relaxation training during the interdialysis period in addition to conventional dialysis treatment. The effect of the intervention was evaluated after 12 weeks. RESULTS: There were no significant differences in the baseline values of various parameters between the two groups. Exercise capacity (sit-to-stand test,handgrip,time to 10 sit-ups) significantly improved in the intervention group after 12 weeks (32.68 ± 8.32 vs 26.50 ± 6.83; 37.42 ± 10.12 vs 28.12 ± 8.51; 19.8 ± 5.40 vs 25.29 ± 7.18) (p < 0.05). In terms of the kidney disease quality of life (KDQOLTM) score, all other dimensions except sexual function, social functioning, burden of kidney disease and work status dimensions showed significant improvement compared to the baseline (p < 0.05). In the control group, only the dialysis staff encouragement (DSE) and patient satisfaction (PS) dimensions showed slight improvements compared to the baseline (p > 0.05). When compared with the control group, the intervention group showed significant improvements in 10 dimensions of exercise capacity and KDQOLTM scores for physical function, role-physical, general health, energy, symptom/problem list, sleep, DSE, pain, cognitive function, emotional well-being and patient PS after 12 weeks (61.30 ± 5.38 vs 42.98 ± 5.73; 57.50 ± 3.55 vs 50.70 ± 3.62) (p < 0.05). Some inflammatory markers, such as the levels of interleukin-6 and high-sensitivity C-reactive protein (30.29 ± 2.96 vs 17.65 ± 3.22; 8.93 ± 0.99 vs 3.02 ± 0.34), showed a decrease during the intervention, while albumin and prealbumin levels were significantly increased compared with the baseline (30.62 ± 1.65 vs 35.60 ± 1.68; 0.32 ± 0.05 vs 0.44 ± 0.07) (p < 0.05). CONCLUSION: Combined intervention training can improve the motor ability and quality of life of patients with sarcopenia within a short period of time.

Mitochondrial bioenergetics: coupling of transport to tubular mitochondrial metabolism.

PURPOSE OF REVIEW: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules. RECENT FINDINGS: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates. We applied EFA assays to freshly isolated mouse proximal tubules, thick ascending limbs (TALs), and distal convoluted tubules (DCTs) and successfully differentiated their unique metabolic features. We found that TALs and DCTs adjusted their mitochondrial bioenergetics and biogenesis in response to acute and chronic alterations of transport activity. Based on the literature and our recent findings, I discuss working models and mechanisms underlying acute and chronic tubular adaptations to transport activity. The potential roles of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) are discussed. SUMMARY: Mitochondria in renal tubules are highly plastic to accommodate different transport activities. Understanding the mechanisms may improve the treatment of renal tubulopathies.

Intermittent tourniquet compared to throughout tourniquet use during Total Knee Arthroplasty in patients with Body Mass Index of 30 or more: A retrospective cohort study.

Background: Tourniquet use during total knee arthroplasty (TKA) reduces bleeding which optimises bone-cement interface for prosthesis stability and improves surgical field visualisation. However, prolonged usage can lead to complications and poorer outcomes. Some surgeons advocate for intermittent tourniquet application. Limited literature exists for patients with high body mass index (BMI). This study aims to compare the outcomes of intermittent tourniquet (IT) to throughout tourniquet (TT) use among obese patients undergoing primary TKA for knee osteoarthritis. Methods: This was a retrospective cohort study. In the TT group, tourniquet was inflated from the beginning and released once the bone cement has hardened. In the IT group, tourniquet was inflated at the beginning, released after initial incision and haemostasis, then inflated again during cementation. Tourniquet was released once the bone cement had set. Categorical outcome measures were analysed using Chi-squared or Fisher's exact test. T-test or Kruskal-Wallis test were used for continuous data. Results: When comparing IT to TT among patients with BMI≥30 (IT n = 48, TT n = 47), the mean duration of surgery was shorter in the TT group (p < 0.05). The difference in haemoglobin drop between the two groups was not statistically significant from post-operative day three onwards. There was no difference in transfusion rate (p > 0.05). ROM was greater in the IT group up to three weeks post-operatively (p < 0.05). When comparing patients with BMI <30 (n = 71) and BMI≥30 (n = 48) with IT use, there was no statistically significant difference in ROM and LOS. Conclusion: Patients with BMI≥30 in the IT group had greater ROM in the initial post-operative period. Although operative time and blood loss were greater among the IT group, there was no difference in transfusion rate. Outcomes of TKA performed with IT were similar for patients with BMI≥30 and BMI <30. The authors recommend intermittent tourniquet use during TKA for patients with BMI≥30. Level of evidence: 3.

Identification of small-molecule binding sites of a ubiquitin-conjugating enzyme-UBE2T through fragment-based screening.

UBE2T is an attractive target for drug development due to its linkage with several types of cancers. However, the druggability of ubiquitin-conjugating E2 (UBE2T) is low because of the lack of a deep and hydrophobic pocket capable of forming strong binding interactions with drug-like small molecules. Here, we performed fragment screening using 19 F-nuclear magnetic resonance (NMR) and validated the hits with 1 H-15 N-heteronuclear single quantum coherence (HSQC) experiment and X-ray crystallographic studies. The cocrystal structures obtained revealed the binding modes of the hit fragments and allowed for the characterization of the fragment-binding sites. Further screening of structural analogues resulted in the identification of a compound series with inhibitory effect on UBE2T activity. Our current study has identified two new binding pockets in UBE2T, which will be useful for the development of small molecules to regulate the function of this protein. In addition, the compounds identified in this study can serve as chemical starting points for the development of UBE2T modulators.

Acceptance of disability in stroke: a systematic review.

BACKGROUND: Evidence for the association between acceptance of disability (AOD) and positive rehabilitation outcomes, as well as for the use of AOD measurements in stroke rehabilitation practice, has increased in the international literature in the last decade. However, measurement tools for AOD are heterogenous and there has not been a systematic review summarizing the current evidence on the use of AOD measures and factors associated with AOD. OBJECTIVE: This study aimed to summarize current evidence on measurement tools used, present existing AOD scores in people with stroke and identify risk factors for and protective factors against poor AOD in people with stroke. METHODS: The original design and protocol of this systematic review were registered with PROSPERO. The included studies were published from 2008 to 2020 and identified from 5 databases-PubMed, EMBASE, CINAHL Plus, PsycInfo, and the Cochrane Library-using the following inclusion criteria: participants diagnosed with stroke and aged ≥16 years, measurement of AOD, and published in English in a peer-reviewed scientific journal. Review articles were excluded. RESULTS: Five measurement tools for AOD were reported. The Revised Acceptance of Disability Scale (ADS-R) and the acceptance subscale of the Illness Cognition Questionnaire (ICQ) had the highest internal consistency. Scores ranged from 71.7 to 74.2 on the ADS-R, 16.9-18.3 on the ICQ, 16.5-26.9 on the Acceptance of Illness Scale, and 87.8-93.2 on the Attitudes towards Disabled Persons Form A. Poorer function and depressive symptoms were associated with poor AOD, whereas religious beliefs, support from others, and an understanding of stroke were associated with better AOD. CONCLUSIONS: The ADS-R and the acceptance subscale of the ICQ are currently the most reliable measurement tools for measuring AOD in people with stroke. Further research to validate the measurement tools is required. This may help to identify people who require additional support. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42017077063; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=77063.

Suspensory Device Fixation of Lisfranc Injuries in a Southeast Asian Urban Population: Patient-Reported Functional Outcomes.

Introduction Open reduction internal fixation (ORIF) and primary arthrodesis are two conventional options for the treatment of Lisfranc injuries. However, they are associated with implant-related complications. An alternative suspensory device construct using interosseous nonabsorbable sutures with endobuttons has been described with satisfactory results. This study aims to explore functional outcomes after suture button fixation of Lisfranc injuries in a Southeast Asian population. Methods This was a single-surgeon retrospective study of patients with Lisfranc injuries treated surgically using a suture button fixation technique between 2017 and 2019. Data collected included demographic information, pre-injury levels of activity, nature of injury, and type of surgery performed. The minimum postoperative follow-up was one year. The Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM) were used to evaluate patient-reported outcomes. Scores were reported in percentage (%) with median and interquartile range. Results Twenty-nine patients with a mean age of 29 years (21-76) were recruited. Sixteen underwent suture button fixation only (SB), and 13 underwent suture button fixation with intercuneiform screw fixation and plating (SBM). The median scores for the FAOS and FAAM questionnaires were at least 80% in all domains. Twenty-eight patients (97%) were able to return to pre-injury activity level, 27 patients (93%) were able to return to sports. Only one patient was not satisfied with the outcomes of surgery. No patients had post-traumatic arthritis or hardware failure necessitating implant removal at the final follow-up. Conclusion This study has demonstrated that treatment of Lisfranc injuries with a suspensory device construct resulted in good outcomes with 97% of patients being able to return to pre-injury activity levels, and 93% of patients being able to return to sports. It may not be necessary to perform primary arthrodesis in uncomplicated Lisfranc injuries. This technique is also advantageous as implant removal is not routinely required due to the design and biomechanical properties of suspensory devices.

Backbone 1H, 15N and 13C resonance assignments for an E2 ubiquitin conjugating enzyme-UBE2T.

Ubiquitin-conjugating enzyme E2 T (UBE2T) plays important roles in ubiquitination of proteins through participation in transferring ubiquitin to its substrate. Due to its importance in protein modifications, UBE2T associates with diverse diseases and serves as an important target for drug discovery and development. The crystal structure of UBE2T has been determined and the structure reveals the lack of a druggable pocket for binding to small molecules for clinical applications. Despite the challenge, effort has been made to develop UBE2T inhibitors. We obtained UBE2T constructs with and without the C-terminal region which is flexible in solution. Herein, we report the backbone resonance assignments for human UBE2T without the C-terminal region. The backbone dynamics of UBE2T was also explored. The available assignments will be helpful for hit identification, determining ligand binding site and understanding the mechanism of action of UBE2T inhibitors.

Stacking Order Induced Anion Redox Regulation for Layer-Structured Na0.75 Li0.2 Mn0.7 Cu0.1 O2 Cathode Materials.

Stacking order plays a key role in defining the electrochemical behavior and structural stability of layer-structured cathode materials. However, the detailed effects of stacking order on anionic redox in layer-structured cathode materials have not been investigated specifically and are still unrevealed. Herein, two layered cathodes with the same chemical formula but different stacking orders: P2-Na0.75 Li0.2 Mn0.7 Cu0.1 O2 (P2-LMC) and P3-Na0.75 Li0.2 Mn0.7 Cu0.1 O2 (P3-LMC) are compared. It is found that P3 stacking order is beneficial to improve the oxygen redox reversibility compared with P2 stacking order. By using synchrotron hard and soft X-ray absorption spectroscopies, three redox couples of Cu2+ /Cu3+ , Mn3.5+ /Mn4+ , and O2- /O- are revealed to contribute charge compensation in P3 structure simultaneously, and two redox couples of Cu2+ /Cu3+ and O2- /O- are more reversible than those in P2-LMC due to the higher electronic densities in Cu 3d and O 2p orbitals in P3-LMC. In situ X-ray diffraction reveals that P3-LMC exhibits higher structural reversibility during charge and discharge than P2-LMC, even at 5C rate. As a result, P3-LMC delivers a high reversible capacity of 190.3 mAh g-1 and capacity retention of 125.7 mAh g-1 over 100 cycles. These findings provide new insight into oxygen-redox-involved layered cathode materials for SIBs.

Scleral growth stunting via sub-Tenon injection of cross-linking solutions in live rabbits.

BACKGROUND: Scleral cross-linking is a potential method to inhibit axial elongation of the eye, preventing the progression of pathological myopia. Formaldehyde releasers, which are common preservatives found in cosmetics and ophthalmic solutions, have been shown to be not only effective in cross-linking corneal collagen in vitro and in vivo, but also have minimal toxicity effects on the eye. The present study aims to evaluate the efficacy of scleral cross-linking using sodium hydroxymethylglycinate (SMG) to inhibit eye growth using an in vivo rabbit model. METHODS: A cross-linking solution containing 40 mM SMG was delivered to the sub-Tenon's space behind the equator. The application regimen included a two-quadrant injection performed five times over 2 weeks on New Zealand White rabbits (n=5, group 1), and one-time injection followed for up to 5 days on Dutch-Belted rabbits (n=6, group 2). Group 1 was monitored serially for axial length changes using B-scan ultrasound for 5-6 weeks. Group 2 was injected with a higher viscosity solution formulation. Both groups were evaluated for thermal denaturation temperature changes of the sclera postmortem. RESULTS: Axial growth was limited by 10%-20% following SMG treatment as compared with the untreated eye. Thermal denaturation analysis showed increased heat resistance of the treated eyes in the areas of injection. Overall, the SMG treatment inhibited eye growth with few side effects from the injections. CONCLUSIONS: Cross-linking solutions delivered via sub-Tenon injection provide a potential method for limiting axial length growth in progressive myopia and could be used as a potential treatment for myopia.

Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.

LncRNA UNC5B-AS1 promotes proliferation and epithelial-mesenchymal transition of cervical cancer cells by regulating Toll-like receptor signaling pathway / 中国药理学通报

Aim To investigate the effects of long non-coding RNA(lncRNA)UNC5B-AS1 on the proliferation and epithelial mesenchymal transformation(EMT)of cervical cancer. Methods GEO and TCGA databases were used to download data sets and differential expression analysis was performed. qRT-PCR was used to verify the differential expression of lncRNA UNC5B-AS1 in normal and cancerous cervical tissues.The interference and overexpression of lncRNA UNC5B-AS1 were transfected into cervical cancer cell lines, and plate cloning, CCK-8 and EdU experiments were used to detect the effect of lncRNA UNC5B-AS1 on the pro-liferation of cervical cancer cells.Transwell assay was used to detect its effect on migration and invasion of cervical cancer cells.The expression levels of EMT-related genes E-Cadherin, N-Cadherin and Vimentin were detected by Western blot. Transcriptome sequencing was used to obtain the signal pathway regulated by lncRNA UNC5B-AS1, and to verify the expression level of related genes. Results RNA microarray and bioinformatics analysis showed that the expression level of lncRNA UNC5B-AS1 in cervical cancer was significantly higher than that in normal cervical tissue, and correlated with the overall survival time of patients.Compared with the negative control group, knockdown lncRNA UNC5B-AS1 could reduce the proliferation, migration and invasion of cervical cancer cells, while overexpression could promote the proliferation, migration and invasion of cervical cancer cells. Western blot showed that lncRNA UNC5B-AS1 could regulate EMT of cervical cancer cells. Transcriptome sequencing showed that lncRNA UNC5B-AS1 could regulate Toll like receptor(TLR)signaling pathway. qRT-PCR and Western blot results showed that the expression levels of TLR-related genes IL-6 and TICAM2 in the knockdown and overexpression lncRNA UNC5B-AS1 group were significantly changed(P<0.05). Conclusions LncRNA UNC5B-AS1 is highly expressed in cervical cancer. Overexpression of lncRNA UNC5B-AS1 may enhance TLR signaling pathway activity, thereby promoting proliferation and EMT of cervical cancer cells.

Rare Manifestations of Common Diseases: Middle-Aged Male Polyuria-Headache-Inflammatory Granulomatous Lesions / 罕见病研究

A middle-aged man was presented with poor appetite, polyuria, polydrpsia, and headache. A sellar mass was found, along with total pituitary hypofunction and visual field defect. A biopsy of the lesion via the trans-sphenoidal approach showed inflammatory changes and granuloma formation. However, repeated cerebrospinal fluid and pathogenic examination of the pathological tissue showed no positive indications. The initial diagnosis considered autoimmune hypophysitis, and treatment of glucocorticoids combined with immunosuppressants was administered, which led to a temporary shrinkage of the lesion, but it gradually enlarged subsequently. After multidisciplinary discussion, a high possibility of pituitary tuberculosis infection was decided upon. After standardized anti-tuberculosis treatment was initiated, the lesion reduced noticeably and the patient′s condition improved. Pituitary tuberculosis infection is incredibly rare and extremely easy to misdiagnose. This case was diagnosed and treated in a timely and effective manner through a multidisciplinary approach, highlighting the importance of such an approach in dealing with rare diseases.

Application prospect of endoscopic ultrasound-guided portal pressure gradient measurement / 临床肝胆病杂志

Portal pressure measurement plays an important role in the diagnosis and evaluation of portal hypertension, and at present, there is still no unified method for the assessment of portal vein pressure. With the wide application of endoscopic ultrasound in digestive system diseases, endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) measurement was included in the research agenda of the 2021 Baveno-VII conference, thus attracting widespread attention of scholars. This article reviews portal pressure measurement techniques, the development of EUS-PPG measurement technique, and two commonly used methods for EUS-PPG measurement in China and globally and elaborates on the application prospect of EUS-PPG measurement technique. A number of studies around the world have shown that EUS-PPG measurement technique is a direct, minimally invasive, simple, accurate, and radiation-free technique with strong clinical operability, and it is an important supplement to portal pressure measurement methods and may gradually become one of the main methods for portal pressure measurement.

Gallbladder microbiota in early vertebrates provides evolutionary insights into mucosal homeostasis.

The gallbladder (GB) microbiota plays critical roles in mammalian metabolism and immune homeostasis, and its relationship with human disease has been extensively studied over the past decade. However, very little is known about the interplay between GB microbiota and the immune functions of teleost fish, the earliest bony vertebrate with a GB. Therefore, this study sought to investigate the composition of the teleost GB microbiota and the potential mechanisms through which it affects mucosal immunity. In our results, we found that the GB mucosa (GM) and bile bacterial community shared a similar microbiological composition with that of the gut mucosa in naïve individuals. IHNV infection induced a profound GB inflammation and disrupted their microbial homeostasis followed by a strong anti-bacterial response. Interestingly, beneficial bacteria from the Lactobacillales order showed a significant increase in the abundance of the bile microbial community, whereas the structure of the Mycoplasmatales order in the gut microbial community was markedly changed. All in all, our study characterized the structure of the GB microbial ecosystem in teleost fish, and the fish GB microbiome shared a high similarity with the gut microbiota. More importantly, our findings offer solid evidence that the teleost GB evolved immune functions to preserve its mucosal microbial homeostasis, suggesting that both the microbiota and mucosal immunity of the GB might have co-evolved in early vertebrates.

Conserved Role of mTORC1 Signaling in B Cell Immunity in Teleost Fish.

Mammalian studies have demonstrated that B cell immune responses are regulated by mechanistic target of rapamycin complex 1 (mTORC1) signaling. Teleost fish represent the oldest living bony vertebrates that contain bona fide B cells. So far, whether the regulatory mechanism of mTORC1 signaling in B cells occurred in teleost fish is still unknown. In this study, we developed a fish model by using rapamycin (RAPA) treatment to inhibit mTORC1 signaling and demonstrated the role of mTORC1 signaling in teleost B cells. In support, we found inhibition of mTORC1 signaling by RAPA decreased the phagocytic capacity, proliferation, and Ig production of B cells. Critically, Flavobacterium columnare induced specific IgM binding in serum, and these titers were significantly inhibited by RAPA treatment, thus decreasing Ab-mediated agglutination of F. columnare and significantly increasing the susceptibility of fish upon F. columnare reinfection. Collectively, our findings elucidated that the mTORC1 pathway is evolutionarily conserved in regulating B cell responses, thus providing a new point for understanding the B cells functions in teleost fish.

The evolution of stomatal traits along the trajectory toward C4 photosynthesis.

C4 photosynthesis optimizes plant carbon and water relations, allowing high photosynthetic rates with low stomatal conductance. Stomata have long been considered a part of the C4 syndrome. However, it remains unclear how stomatal traits evolved along the path from C3 to C4. Here, we examined stomata in the Flaveria genus, a model used for C4 evolutionary study. Comparative, transgenic, and semi-in vitro experiments were performed to study the molecular basis that underlies the changes of stomatal traits in C4 evolution. The evolution from C3 to C4 species is accompanied by a gradual rather than an abrupt change in stomatal traits. The initial change appears near the Type I intermediate stage. Co-evolution of the photosynthetic pathway and stomatal traits is supported. On the road to C4, stomata tend to be fewer in number but larger in size and stomatal density dominates changes in anatomical maximum stomatal conductance (gsmax). Reduction of FSTOMAGEN expression underlies decreased gsmax in Flaveria and likely occurs in other C4 lineages. Decreased gsmax contributes to the increase in intrinsic water-use efficiency in C4 evolution. This work highlights the stomatal traits in the current C4 evolutionary model. Our study provides insights into the pattern, mechanism, and role of stomatal evolution along the road toward C4.