Primary immunodeficiency as a cause of immune-mediated kidney diseases.

Primary immunodeficiency (PID) is no longer defined by infections alone, and autoimmunity is an accompanying manifestation of PID. Recurrent infections may trigger autoimmunity through molecular mimicry, bystander activation, or superantigens. The diagnosis of PID is still challenging, but genetic analysis reveals the underlying link between PID and autoimmunity. Mutations in relevant genes affecting central and peripheral immune tolerance, regulatory T-cell function, expansion of autoreactive lymphocytes, antigen clearance, hyperactivation of type I interferon, and NF-κB pathways have all been implicated in triggering autoimmunity in PID. Autoimmunity in PID leads to chronic inflammation, tissue damage, and organ failure and increases the mortality of patients with PID. The kidneys are inextricably linked with the immune system, and kidney diseases can be mediated by both infection and autoimmunity/inflammation in PID patients. The manifestations of kidney involvement in PID patients are very heterogeneous and include lupus nephritis, C3 glomerulopathy, kidney thrombotic microangiopathy, vasculitis, and interstitial nephritis.Patients with PID-caused kidney diseases have defined immune function defects and may benefit from pathway-based biologics, stem cell transplantation, or gene therapy. Early diagnosis and appropriate treatment of PID are crucial for reducing the mortality rate and improving organ function and quality of life.

Fast 3D positioning based on a simplified THz photonic stereo ISAR system.

In this work, a THz stereo inverse synthetic aperture radar scheme based on photonics is proposed, and proof-of-concept experimentally demonstrated, achieving high resolution and fast three-dimensional (3D) positioning of multiple targets. An optical frequency comb and a uni-traveling carrier photodiode are employed to photonically generate a linear frequency-modulation signal at 300-320 GHz. By two incoherent measurements at different angles with one pair of antennas, 3D positioning of plane reflectors over a distance of 0.6 m is successfully accomplished, achieving a resolution of 7.5 mm for both range and azimuth dimensions, and a maximum experimental height error of 4 mm.

Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation.

BACKGROUND: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes of LN can facilitate more individual treatment strategies. METHODS: We performed whole-exome sequencing in a cohort of Chinese patients with LN and identified variants of a disease-causing gene. Extensive biochemical, immunologic, and functional analyses assessed the effect of the variant on type I IFN signaling. We further investigated the effectiveness of targeted therapy using single-cell RNA sequencing. RESULTS: We identified a novel DDX58 pathogenic variant, R109C, in five unrelated families with LN. The DDX58 R109C variant is a gain-of-function mutation, elevating type I IFN signaling due to reduced autoinhibition, which leads to RIG-I hyperactivation, increased RIG-I K63 ubiquitination, and MAVS aggregation. Transcriptome analysis revealed an increased IFN signature in patient monocytes. Initiation of JAK inhibitor therapy (baricitinib 2 mg/d) effectively suppressed the IFN signal in one patient. CONCLUSIONS: A novel DDX58 R109C variant that can cause LN connects IFNopathy and LN, suggesting targeted therapy on the basis of pathogenicity. PODCAST: This article contains a podcast at.

Variations in mitochondrial DNA coding and D-loop region are associated with early embryonic development defects in infertile women.

Mitochondrial DNA (mtDNA) plays a critical role in oocyte maturation, fertilization, and early embryonic development. Defects in mtDNA may determine the alteration of the mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply, leading to impaired oocyte maturation, abnormal fertilization, and low embryonic developmental potential, ultimately leading to female infertility. This case-control study was established to investigate the correlation between mtDNA variations and early embryonic development defects. Peripheral blood was collected for next-generation sequencing from women who suffered the repeated failures of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) cycles due to early embryonic development defects as well as in-house healthy controls, and the sequencing results were statistically analyzed for all subjects. This study found that infertile women with early embryonic development defects carried more mtDNA variants, especially in the D-loop region, ATP6 gene, and CYTB gene. By univariate logistic regression analysis, 16 mtDNA variants were associated with an increased risk of early embryonic development defects (OR > 1, p < 0.05). Furthermore, we identified 16 potentially pathogenic mtDNA variants only in infertile cases. The data proved that mtDNA variations were associated with early embryonic development defects in infertile Chinese women.

Robot-assisted percutaneous balloon compression for trigeminal neuralgia- preliminary experiences.

OBJECTIVES: This study aims to discuss the availability of robot-assisted percutaneous balloon compression (PBC) for trigeminal neuralgia (TN) and share our preliminary experiences. METHODS: Patients with TN who underwent robot-assisted PBC from June to September 2022 were enrolled. We designed a fixing plug for robot-assisted PBC, three-dimensional structured light registration was used, puncture trajectory was the line connects the medial third of inner and outer aperture of foramen ovale. Numerical Rating Scale (NRS), Barrow Neurological Institute (BNI) pain and numbness intensity score were used to evaluate the facial pain and numbness. RESULTS: Eventually, nine patients were enrolled, the structured light registrations were successfully finished in all patients with a mean registration error of 0.68 mm. All the punctures of foramen ovales were successfully done one-time. Of note, the balloons were all got pear-shaped followed by 150 to 180 s compression. Though, postoperatively, all the patients complained of facial numbness and four patients suffered from transient masseter weakness, all patients got fully or mostly pain relief. It should be noted that is the numbness and weakness gradually relieved during follow-up. CONCLUSION: Three-dimensional structured light registration and robot assisted PBC is an effective choice for patients with TN. Extension line between the medial third of the inner and outer aperture of foramen ovale might be a safe and effective puncture trajectory to this procedure.

The Effect of Surgical Positioning on Pneumocephalus in Subthalamic Nucleus Deep Brain Stimulation Surgery for Parkinson Disease.

OBJECTIVES: This research analyzed the effect of surgical positioning on postoperative pneumocephalus and assessed additional potential risk factors of pneumocephalus in subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). MATERIALS AND METHODS: In this study, 255 consecutive patients with PD who received bilateral STN DBS under general anesthesia were retrospectively included. Of these, 180 patients underwent surgery with their heads in an elevated position, and 75 patients underwent surgery in a supine position. The postoperative pneumocephalus volume was compared between the two groups. Other potential risk factors for pneumocephalus also were analyzed. RESULTS: The mean pneumocephalus volume for the group with elevated-head positioning (16.76 ± 15.23 cm3) was greater than for the supine group (3.25 ± 8.78 cm3) (p < 0.001). Multivariable analysis indicated that the pneumocephalus volume was related to surgical positioning, lateral trajectory angle, intraoperative mean arterial pressure (MAP), microelectrode recording (MER) passage number, brain atrophy degree, and the anterior trajectory angle. No correlation was found between pneumocephalus and age, sex, duration of PD, surgery length, or intracranial volume. In the subgroup analysis, the pneumocephalus volume exhibited a negative correlation with intraoperative MAP (r = -0.210, p = 0.005) and positive correlations with degree of brain atrophy (r = 0.242, p = 0.001) and MER passage number (r = 0.184, p = 0.014) in the elevated-head group. Specifically, an MER passage number > 3 was a significant risk factor for pneumocephalus in the elevated-head group. A positive correlation was observed between the pneumocephalus volume and the lateral trajectory angle in both groups (elevated-head positioning, r = 0.153, p = 0.041; supine positioning, r = 0.546, p < 0.001). CONCLUSIONS: In patients with PD who were anesthetized and receiving STN DBS, supine positioning reduced pneumocephalus volume compared with patients with PD receiving STN DBS with their heads elevated. The pneumocephalus volume was negatively correlated with intraoperative MAP and positively correlated with the degree of brain atrophy, the lateral trajectory angle, and the MER passage number.

A Potential Adhesin/Invasin STM0306 Participates in Host Cell Inflammation Induced by Salmonella enterica Serovar Typhimurium.

Salmonella enterica serovar typhimurium (S. Typhimurium) is a common Gram-negative foodborne pathogenic bacterium that causes gastrointestinal disease in humans and animals. It is well known that adhesins and invasins play crucial roles in the infection mechanism of S. Typhimurium. S. Typhimurium STM0306 has been denoted as a putative protein and its functions have rarely been reported. In this study, we constructed the STM0306 gene mutant strain of S. Typhimurium and purified the recombinant STM0306 from Escherichia coli. Deletion of the STM0306 gene resulted in reduced adhesion and invasion of S. Typhimurium to IPEC-J2, Caco-2, and RAW264.7 cells. In addition, STM0306 could bind to intestinal epithelial cells and induced F-actin modulation in IPEC-J2 cells. Furthermore, we found that STM0306 activated the nuclear factor kappa B (NF-κB) signaling pathway and increased the mRNA expression of pro-inflammatory cytokines such as IL-1ß, TNF-α, as well as chemokine CXCL2, thus resulting in cellular inflammation in host cells. In vivo, the deletion of the STM0306 gene led to reduced pathogenicity of S. Typhimurium, as evidenced by lower fecal bacterial counts and reduced body weight loss in S. Typhimurium infected mice. In conclusion, the STM0306 of S. Typhimurium is an important adhesin/invasin involved in the pathogenic process and cellular inflammation of the host.

MicroRNA-27a inhibits porcine type I muscle fibre gene expression by directly targeting peroxisome proliferator-activated receptor-γ coactivator-1α.

MicroRNAs are one of the key determinants of muscle fibre development and phenotype in mammals. The preliminary experiment implied that microRNA-27a (miR-27a) might involve in regulation of muscle fibre type composition of pigs. Thereby, the present study aimed to confirm the regulatory effect of miR-27a on porcine type I muscle fibre-encoding gene (myosin heavy chain gene 7, MYH7) expression and its related mechanism. We firstly observed opposite expression patterns between miR-27a and MYH7 as well as between miR-27a and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) during differentiation of porcine skeletal muscle satellite cells. Through the subsequent transfection analysis in porcine myotubes, we found that miR-27a suppressed the expression of MYH7 and PGC-1α. Besides, miR-27a induced inhibition of PGC-1α downstream targets, namely myocyte enhancer factor-2C (MEF2C) along with mitochondrial biogenesis and oxidative metabolism-related factors such as nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), cytochrome c (Cytc) and cytochrome oxidase IV (COX Ⅳ) and succinodehydrogenase (SDH). Dual-luciferase reporter analysis revealed that miR-27a could bind to the predicted target site in the 3'-untranslated regions of PGC-1α mRNA, confirming a direct targeting of PGC-1α by miR-27a. Moreover, PGC-1α silencing abolished the promotive effects of miR-27a inhibitor on MYH7, PGC-1α and its downstream targets (MEF2C, NRF-1, mtTFA, COX Ⅳ, Cytc and SDH) in porcine myotubes. Collectively, miR-27a inhibits porcine MYH7 expression by negatively regulating PGC-1α and PGC-1α-controlled MEF2C expression as well as mitochondrial biogenesis and oxidative metabolism. Our findings may provide a molecular target for genetic or nutritional control of muscle fibre phenotype of pigs, probably having an important implication for regulating pork quality.

Theoretical insights into effective electron transfer and migration behavior for CO2 reduction on the BiOBr(001) surfaces.

Carbon dioxide (CO2) activation by effective electrons has been regarded as the rather necessary first-step for a CO2 reduction reaction (CO2RR). In addition, the electron migration and photoreaction selectivity are closely associated with the dominant crystal surface of a catalyst. Therefore, it is very interesting and important to elucidate the electron transfer and charge density effects on the catalyst surface for the CO2RR. In this work, the dominant highly-active BiOBr(001) surfaces with Bi-, O- and Br-termination atoms are designed so that their electron distributions and CO2RR behaviors can be observed. The electron-rich sites on the BiOBr(001) surfaces, where more effective electrons will migrate to achieve the activation of the adsorbed CO2, are firstly confirmed by the electron density difference based on density functional theory calculations. Next, the CO2RR pathways at the electron-rich sites are investigated to explore the migration mechanism of effective photo-induced electrons. The results obtained reveal that if a larger number of electrons transfer to CO2, then less energy is needed to break the CO bond, and the formation of a *COOH intermediate corresponds to the ability of the surface to take part in protonation. Furthermore, the interface Bi atom can boost the transfer efficiency of effective electrons to CO2, but the exposed Br atom with a longer electron transfer distance, because of the steric hindrance of the interface Br atoms, makes it difficult for the electrons to migrate, resulting in it being harder to fracture the CO bond to benefit the formation of the HCOOH product. These findings should give deep insight into the migration behaviors of effective electrons for CO2 photoreduction on the BiOBr(001) surface and provide new perspectives for better understanding the structure-performance relationship at the molecular level.

Channel Model and Performance Analysis for MIMO Systems with Single Leaky Coaxial Cable in Tunnel Scenarios.

Due to the limited space in the tunnel environment, multiple-input multiple-output (MIMO) systems with double-port fed leaky coaxial cables (LCXs) can not only reduce the number of LCXs, but also improve the channel capacity. Based on the geometry based on single bonce (GBSB) and electromagnetic field radiation theory of LCX, a MIMO channel model with double-port fed LCX in a tunnel scenario is proposed in this paper. The channel impulse response (CIR) is derived, and verified with measurement results in terms of channel capacity. The distribution of channel capacity of single double-port fed LCX under different LCX lengths in the tunnel scenarios has also been analyzed in this work, and the distribution of channel capacity for the LCX-MIMO system with long LCX is predicted. The results show that the single double-port fed LCX-MIMO system outperforms the dipole antenna MIMO system with respect to channel capacity in the considered tunnel scenarios.

Triallyl Isocyanurate as an Efficient Electrolyte Additive for Layered Oxide Cathode Material-Based Lithium-Ion Batteries with Improved Stability under High-Voltage.

In this study, a new electrolyte additive 1,3,5-tri-2-propenyl-1,3,5-triazine-2,4,6-(1H, 3H, 5H)-trione (TAIC) for lithium-ion batteries is reported. The additive is introduced as a novel electrolyte additive to enhance electrochemical performances of layered lithium nickel cobalt manganese oxide (NCM) and lithium cobalt oxide (LiCoO2) cathodes, especially under a higher working voltage. Encouragingly, we found protective films would be formed on the cathode surface by the electrochemical oxidation, and the stability of the cathode material-electrolyte interface was greatly promoted. By adding 0.5 wt.% of TAIC into the electrolyte, the battery exhibited outstanding performances. The thickness swelling decreased to about 6% after storage at 85 °C for 24 h, while the capacity retention of cycle-life performances under high temperature of 45 °C after the 600th cycle increased 10% in comparison with the batteries without TAIC. Due to its specific function, the additive can be used in high energy density and high voltage lithium-ion battery systems.

Mutation analysis of tubulin beta 8 class VIII in infertile females with oocyte or embryonic defects.

Variants of tubulin beta 8 class VIII (TUBB8) have been shown to be associated with female infertility characterized by oocyte or embryonic defects. To further investigate the mutational spectrum of TUBB8 and the prevalence of variants, we performed Sanger sequencing of TUBB8 on a total of 115 infertile females who had undergone repeated in vitro fertilization cycles with oocyte or embryonic defects and 200 healthy controls. A total of 31 variants which were absent from the controls were identified in 36 unrelated individuals, accounting for a large proportion of this cohort (31.3%). All of the variants including heterozygous/homozygous missense variants and a heterozygous frameshift insertion variant were at conserved sites and predicted to be deleterious. Besides, these variants had diverse phenotypic effects, including not only oocyte maturation arrest, fertilization failure, and early embryonic arrest, but also multi-pronuclei (MPN) formation, which is a new phenotype associated with TUBB8 variants. Overall, this study reveals a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects. Our results not only broaden the mutational and phenotypic spectra of TUBB8 variants, but also further confirm the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development.

The altered immunological status of children conceived by assisted reproductive technology.

BACKGROUND: With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. METHODS: A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. RESULTS: Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = - 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). CONCLUSIONS: Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.

Ultrasound-Guided Retrograde Infrapopliteal Artery Access for Recanalization of Complex Femoral-Popliteal Artery Occlusions.

BACKGROUND: The aim of the study was to review the outcomes of femoral-popliteal artery (FPA) interventions using an ultrasound (US)-guided retrograde infrapopliteal artery access after the failure of an antegrade recanalization. METHODS: From Jan 2016 to Jan 2019, 37 patients with chronic total occlusion (CTO) of the FPA underwent ultrasound (US)-guided retrograde infrapopliteal artery access after failure of an antegrade procedure. Treated limbs were classified as Rutherford class 5 or 6 (29.7%) and class 4 (62.2%). Data collected included success rate and time to access using US. Immediate in-hospital and follow-up outcomes were also documented. RESULTS: US-guided retrograde infrapopliteal artery access was successful in 100% of the patients (anterior tibial = 11, posterior tibial = 19, Peroneal = 4, Dorsalis pedis = 3). Retrograde revascularization was achieved in all 37 patients (100%) using balloon angioplasty (17/37, 45.9%) and additional stent placement (20/37, 54.1%). Ankle-brachial index (ABI) measurements changed from 0.25 ± 0.1 preinterventionally to 0.75 ± 0.07 at 1 day postinterventionally (<0.001). Minor complications occurred in 2/37 patients (5.4%) including one bleeding and vasospasm at the posterior tibial artery, both of which were treated conservatively. No patient experienced access-related thrombosis, aneurysm, compartment syndrome or death. Thirty of 37 (81%) patients completed for at least 12 months of follow-up. None of the successful revascularized patients had major or minor amputations during the follow-up period. CONCLUSIONS: US-guided retrograde infrapopliteal artery access is a safe and successful technique, which expands revascularization options after the failure of conventional endovascular antegrade approaches.

LINC00973 is involved in cancer immune suppression through positive regulation of Siglec-15 in clear-cell renal cell carcinoma.

The pioneering work from Lieping Chen's laboratory identified Siglec-15 as a novel tumor immune suppressor, while the regulatory mechanisms underlying the broad upregulation of Siglec-15 in human cancers remain obscure. Here we found that long non-coding RNA (lncRNA) LINC00973 was higher in Siglec-15-positive clear-cell renal cell carcinoma (ccRCC), and LINC00973 positively regulated Siglec-15 expression at transcriptional level. This effect was evidently dependent on miR-7109-3p (designated as miR-7109 hereafter), and we provided evidence that Siglec-15 is a direct target of miR-7109. Through sponging miR-7109, LINC00973 functioned as competing endogenous RNA (ceRNA) to control cell surface abundance of Siglec-15, and, consequently, was involved in cancer immune suppression. We further demonstrated that LINC00973 and miR-7109 expression in ccRCC antagonistically influenced immune activation of co-cultured Jurkat cells. Our study highlighted the importance of LINC00973-miR-7109-Siglec-15 in immune evasion in ccRCC, which offers significant opportunity for both therapeutic intervention and diagnostic/prognostic exploitations.

Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy.

BACKGROUND: Recent data suggest that miR-196a is predominantly expressed in the kidney and plays an inhibitory role in the progress of renal interstitial fibrosis (IF). However, the predictive value of miR-196a in diabetic nephropathy (DN) remains unknown. We validated the role of urinary miR-196a in the progression of renal injury in a cohort of patients with type 2 diabetes mellitus. METHODS: Our study included 209 patients with biopsy-proven DN. The mean follow-up time was 54.03 ± 32.94 months. Histological lesions were assessed using the pathological classification established by the Renal Pathology Society. Percentages of IF and tubular atrophy were assessed using the Aperio ScanScope system. We measured the correlation of urinary miR-196a with clinical and pathological parameters using the Spearman's correlation test. The influence of urinary miR-196a on renal outcomes was assessed using Cox regression analysis. RESULTS: Urinary miR-196a levels correlated positively with proteinuria (ρ = 0.385, P < 0.001), duration of diabetes mellitus (ρ = 0.255, P < 0.001) and systolic blood pressure (ρ = 0.267, P < 0.001). The baseline estimated glomerular filtration rate (eGFR) and hemoglobin level showed a negative correlation with urinary miR-196a (ρ = -0.247, P < 0.001 and ρ = -0.236, P = 0.001, respectively). Pathologically, urinary miR-196a levels correlated with glomerular sclerosis and IF in patients with DN. Urinary miR-196a was significantly associated with progression to end-stage renal disease [hazard ratio (HR) 2.03, P < 0.001] and a 40% reduction of baseline eGFR (HR 1.75, P = 0.001), independent of age, gender, body mass index, mean arterial pressure and hemoglobinA1c level. However, urinary miR-196a did not improve predictive power to proteinuria and eGFR in DN patients. CONCLUSIONS: Increased urinary miR-196a was significantly associated with the progression of renal injury and might be a noninvasive prognostic marker of renal fibrosis in DN patients.

Effectiveness and long-term outcomes of different crossing strategies for the endovascular treatment of iliac artery chronic Total occlusions.

BACKGROUND: The iliac occlusive disease is usually treated with endovascular procedures in recent years. The effectiveness of different crossing approaches for these occlusions is not precisely known. We performed a retrospective study to explore the optimal crossing approach (antegrade versus retrograde) for iliac artery chronic total occlusions (CTOs) and to examine the long-term outcomes. MATERIALS AND METHODS: We performed a study on 107 patients (116 iliac occlusive lesions, mean age 64.0 ± 11.1, 88 men) who underwent an iliac CTO endovascular intervention attempted with the use of both crossing strategies but were managed with one final crossing approach between August 2012 and August 2018. Baseline data, procedural characteristics, and outcomes were described. A Cox proportional hazard model and Kaplan-Meier method were developed to assess the differences in the two crossing approaches in terms of the 1-year and 5-year primary patency rates, target lesion revascularization (TLR) and major adverse limb events (MALEs). RESULTS: Common iliac artery (CIA) lesions were more likely to be crossed successfully in the retrograde direction (6.8% for antegrade vs. 20.9% for retrograde, p = 0.005), while lesions in the CIA/ external iliac artery (EIA) were more prone to be crossed successfully in the antegrade direction (58.9% for antegrade vs. 39.5% for retrograde, p = 0.016). There were no significant differences in the crossing approach for EIA lesions between the two groups. The two crossing approaches were associated with similar estimates of 1- and 5-year primary patency, TLR and MALE rates. CONCLUSION: The antegrade approach was associated with a higher rate of successful crossing in CIA/EIA CTO lesions, while the CIA-only CTOs were more likely to be crossed successfully with the retrograde approach.

Overexpression of lncRNA snaR is correlated with progression and predicts poor survival of laryngeal squamous cell carcinoma.

Long noncoding RNAs (lncRNA) snaR is a characterized oncogenic lncRNA in triple negative breast cancer and ovarian cancer, while its role in other human diseases is unknown. In the present study, we found that plasma levels of snaR were upregulated in patients with laryngeal squamous cell carcinoma (LSCC) than in healthy controls. Plasma levels of snaR increased with increase in AJCC stages. Follow-up study showed that high plasma levels of snaR were correlated with poor overall survival. Plasma levels of snaR were positively correlated with transforming growth factor beta (TGF-ß1) in patients with LSCC but not in healthy controls. Overexpression of snaR resulted in upregulation of TGF-ß1 in cells of human LSCC cell lines, while exogenous TGF-ß1 treatment showed no significant effect on snaR expression. snaR overexpression and exogenous TGF-ß1 treatment promoted LSCC cell proliferation, migration, and invasion. In addition, TGF-ß inhibitor partially reduced the enhancing effects of snaR overexpression on LSCC cell proliferation, migration, and invasion. Therefore, overexpression of lncRNA snaR is correlated with progression and predicts poor survival of LSCC and the mechanism of its actions is likely related to TGF-ß1.

Theoretical insights into photo-induced electron transfer at BiOX (X = F, Cl, Br, I) (001) surfaces and interfaces.

The electron transfer process (ETP) of a photocatalyst plays a crucial role in clarifying its photoelectrochemical catalytic mechanism. BiOX (X = F, Cl, Br, I) (001) surfaces display excellent photocatalytic performance due to the high separation efficiency of photogenerated electron-hole (e--h+) pairs in their own efficient internal electric field (IEF). The oxygen vacancies (OVs) on the surfaces could cause a change in localized electronic states, then improve the photocatalytic activity of BiOX. Here, the ETP at BiOX (001) surfaces with and without surface OVs were calculated and investigated using a DMol3 module based on density functional theory (DFT). The results showed that the electron transfer at the BiOX (001) surfaces and interfaces should be like this: firstly, the [-O-Bi-] layer at the interface received the photon energy, which made the electrons on the O atoms preferentially photo-induced to Bi atoms and left photo-induced holes on the interface O atoms. Then, the effective electrons on the interface Bi atoms were diffused to one- or multi- electron reactions, and at the same time, electrons from the bulk were transferred through the path of O → Bi → X → X → Bi → O on BiOX (001) surfaces under the IEF effect to interface O atoms, and consequently, maintain the stable proceeding of the photocatalytic reaction. More importantly, we found that the X atoms indeed played a key role in connecting the non-bonding interlayers of the BiOX nanocrystals and affecting the ETP on BiOX (001) surfaces as electron transmitters. The exploration of the OV introduction on BiOX (001) surfaces suggested that the OV-induced localized electronic states should increase the electron mobility and the charge carrier density to improve the photocatalytic activity of BiOX, especially for BiOCl and BiOBr. Our findings could provide new insight for deeply understanding the transfer and catalytic behaviour of photo-induced electrons at BiOX (001) surfaces and interfaces.

Urinary miR-196a predicts disease progression in patients with chronic kidney disease.

BACKGROUND: Urinary miRNAs may potentially serve as noninvasive biomarkers in various kidney diseases to reflect disease activity, severity and progression, especially those correlated with the pathogenesis of kidney diseases. This study demonstrates that urinary miR-196a, a kidney-enriched miRNA, can predict progression of chronic kidney disease (CKD). METHODS: Focal segmental glomerulosclerosis (FSGS) cohorts were used as the representative example of CKD. First, correlation of miR-196a with disease activity was analyzed using paired urine and plasma samples from FSGS patients with nephrotic-range proteinuria (FSGS-A), complete remission (FSGS-CR) and normal controls (NCs). Then, the value of urinary miR-196a in predicting disease progression was validated using another cohort of 231 FSGS patients who were followed-up until over 36 months or reaching end-stage renal disease (ESRD). MiR-196a levels were analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS: The results showed that urinary miR-196a significantly increased in FSGS-A compared with FSGS-CR and NCs, clearly distinguishing FSGS-A from FSGS-CR and NCs, whereas plasma miR-196a showed no difference among these groups. Moreover, urinary miR-196a, which was associated with proteinuria, estimated glomerular filtration rate (eGFR), interstitial fibrosis and tubular atrophy, significantly increased in patients progressed to ESRD compared to those not. Furthermore, patients with higher urinary miR-196a displayed poorer renal survival than those with lower urinary miR-196a. Multivariate Cox analysis confirmed urinary miR-196a as an independent risk factor for FSGS progression after adjusting for age, sex, proteinuria and eGFR. Prediction accuracy of ESRD was significantly improved by combining urinary miR-196a with other indicators including eGFR and proteinuria. CONCLUSION: Urinary miR-196a may serve as a biomarker for predicting CKD progression.