Heterogeneity of mature oligodendrocytes in the central nervous system.

ABSTRACT: Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking. We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes. Indeed, recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences. Furthermore, modern molecular investigations, employing techniques such as single cell/nucleus RNA sequencing, consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region. Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis, Alzheimer's disease, and psychiatric disorders. Nevertheless, caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations. Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity. Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species, sex, central nervous system region, age, and disease, hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Age-dependent effects of metformin on human oligodendrocyte lineage cell ensheathment capacity.

Metformin restores the myelination potential of aged rat A2B5+ oligodendrocyte progenitor cells and may enhance recovery in children with post-radiation brain injury. Human late progenitor cells (O4+A2B5+) have a superior capacity to ensheath nanofibres compared to mature oligodendrocytes, with cells from paediatric sources exceeding adults. In this study, we assessed the effects of metformin on ensheathment capacity of human adult and paediatric progenitors and mature oligodendrocytes and related differences to transcriptional changes. A2B5+ progenitors and mature cells, derived from surgical tissues by immune-magnetic separation, were assessed for ensheathment capacity in nanofibre plates over 2 weeks. Metformin (10 µM every other day) was added to selected cultures. RNA was extracted from treated and control cultures after 2 days. For all ages, ensheathment by progenitors exceeded mature oligodendrocytes. Metformin enhanced ensheathment by adult donor cells but reduced ensheathment by paediatric cells. Metformin marginally increased cell death in paediatric progenitors. Metformin-induced changes in gene expression are distinct for each cell type. Adult progenitors showed up-regulation of pathways involved in the process of outgrowth and promoting lipid biosynthesis. Paediatric progenitors showed a relatively greater proportion of down- versus up-regulated pathways, these involved cell morphology, development and synaptic transmission. Metformin-induced AMP-activated protein kinase activation in all cell types; AMP-activated protein kinase inhibitor BML-275 reduced functional metformin effects only with adult cells. Our results indicate age and differentiation stage-related differences in human oligodendroglia lineage cells in response to metformin. Clinical trials for demyelinating conditions will indicate how these differences translate in vivo.

Clinical characteristics and risk factors of non-mild outcomes in patients with Omicron variant COVID-19 in Shanghai, China.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China in early March 2022. Although a few studies have analyzed the risk factors of the severe type, identifying risk factors for non-mild COVID-19 outcomes (general/severe/critical type) which occur with radiographic evidence of pneumonia is lacking. METHODOLOGY: The COVID-19 patients admitted to a district-level designated hospital from April 26 to May 21 were enrolled in this retrospective study. The clinical manifestations and laboratory examinations were analyzed. Logistic regression was employed to evaluate risk factors for non-mild outcomes. RESULTS: Of the 311 patients, 196 (63.0%) were mild and 115 (37.0%) were non-mild. Among them, 215 cases (69.1%) were unvaccinated. Male, ≥ 60 years age, and chronic kidney disease were risk factors of progressing to non-mild. Patients with more than two comorbidities were more likely to become non-mild, whereas two/booster doses vaccinated patients had a lower risk of developing to non-mild. The median negative conversion days (NCDs) were 12 days. Non-mild, > 2 comorbidities, delayed admission (> 3 days), and Paxlovid (Pfizer, Freiburg, Germany) treatment significantly lengthened the NCDs. CONCLUSIONS: Our results call for special concern for full and booster vaccination of the elderly, which will effectively protect from progression of COVID-19 to non-mild state. In the meantime, symptomatic COVID-19 patients should be treated as soon as possible.

Ultrasound diagnosis and treatment of branchial cleft cyst and preoperative management.

OBJECTIVE: The ultrasonic diagnosis of cervical and facial cystic masses, as well as cases of missed diagnosis and misdiagnosis, was examined, to improve the diagnosis of branchial cleft anomalies. METHODS: A retrospective analysis was conducted on 17 patients with branchial cleft cyst anomalies, including 11 males and 6 females, aged 12-53 years, with an average age of 33 ± 2 years, were unilateral single. All patients who underwent an ultrasound examination and image storage for retrospective analysis, and both longitudinal and transverse sections were scanned to observe the shape, size, boundary, peripheral relationship, and blood flow signal of the masses. All cases were examined with an enhanced CT scan, and pathological reports were generated. RESULTS: Among the 17 cases of branchial cleft anomalies, 15 cases were branchial cleft cysts, while one case involved fistula formation and one case involved sinus tract formation. Based on the type of branchial cleft, the first, second, and third cysts were classified in 4, 12, and 1 case, respectively. The sensitivity rate and specificity of ultrasonic diagnosis were 14/17 (82.4%) and 4/6 (66.7%), respectively. Ultrasonic characteristic analysis for the masses can be found in simple cystic masses or hypoechoic masses, most of them are of a regular shape and have a distinct boundary, and almost no blood flow signal. All patients who were misdiagnosed exhibited blood flow signals, including 1 patient with an abundant blood flow signal, 1 patient suspected of having ectopic thyroid with an abnormal function due to the rat-tail sign, 2 patients misdiagnosed as local inflammatory focus, and 1 patient misdiagnosed with tuberculous lymphadenitis. CONCLUSION: Ultrasound has a detection rate of up to 100% for cervical and facial masses, providing a fundamental determination of lesion characteristics and specific guidance for preoperative diagnosis. If the blood flow signals can be identified and carefully considered their peripheral relationship, the diagnostic rate can be improved.

Role of N6-methyladenosine methylation in glioma: recent insights and future directions.

Glioma is the most pervasive intracranial tumor in the central nervous system (CNS), with glioblastoma (GBM) being the most malignant type having a highly heterogeneous cancer cell population. There is a significantly high mortality rate in GBM patients. Molecular biomarkers related to GBM malignancy may have prognostic values in predicting survival outcomes and therapeutic responses, especially in patients with high-grade gliomas. In particular, N6-methyladenine (m6A) mRNA modification is the most abundant form of post-transcriptional RNA modification in mammals and is involved in regulating mRNA translation and degradation. Cumulative findings indicate that m6A methylation plays a crucial part in neurogenesis and glioma pathogenesis. In this review, we summarize recent advances regarding the functional significance of m6A modification and its regulatory factors in glioma occurrence and progression. Significant advancement of m6A methylation-associated regulators as potential therapeutic targets is also discussed.

HMGB2 Deficiency Mitigates Abdominal Aortic Aneurysm by Suppressing Ang-II-Caused Ferroptosis and Inflammation via NF-κß Pathway.

Background: Ferroptosis is a new form of cell death, which is closely related to the occurrence of many diseases. Our work focused on the mechanism by which HMGB2 regulate ferroptosis and inflammation in abdominal aortic aneurysm (AAA). Methods: Reverse transcription-quantitative polymerase chain reaction and western blot were utilized to assess HMGB2 levels. CCK-8 and flow cytometry assays were utilized to measure cell viability and apoptosis. We detected reactive oxygen species generation, Fe2+ level, and ferroptosis-related protein levels in Ang-II-treated VSMCs, which were typical characteristics of ferroptosis. Finally, the mice model of AAA was established to verify the function of HMGB2 in vivo. Results: Increased HMGB2 level was observed in Ang-II-treated VSMCs and Ang-II-induced mice model. HMGB2 depletion accelerated viability and impeded apoptosis in Ang-II-irritatived VSMCs. Moreover, HMGB2 deficiency neutralized the increase of ROS in VSMCs caused by Ang-II. HMGB2 silencing considerably weakened Ang-II-caused VSMC ferroptosis, as revealed by the decrease of Fe2+ level and ACSL4 and COX2 levels and the increase in GPX4 and FTH1 levels. Furthermore, the mitigation effects of shHMGB2 on Ang-II-induced VSMC damage could be counteracted by erastin, a ferroptosis agonist. Mechanically, HMGB2 depletion inactivated the NF-κß signaling in Ang-II-treated VSMCs. Conclusions: Our work demonstrated that inhibition of HMGB2-regulated ferroptosis and inflammation to protect against AAA via NF-κß signaling, suggesting that HMGB2 may be a potent therapeutic agent for AAA.

Frontoparietal network homogeneity as a biomarker for mania and remitted bipolar disorder and a predictor of early treatment response in bipolar mania patient.

OBJECTIVE: Previous studies have revealed the frontoparietal network (FPN) plays a key role in the imaging pathophysiology of bipolar disorder (BD). However, network homogeneity (NH) in the FPN among bipolar mania (BipM), remitted bipolar disorder (rBD), and healthy controls (HCs) remains unknown. The present study aimed to explore whether NH within the FPN can be used as an imaging biomarker to differentiate BipM from rBD and to predict treatment efficacy for patients with BipM. METHODS: Sixty-six patients with BD (38 BipM and 28 rBD) and 60 HCs participated in resting-state functional magnetic resonance imaging and neuropsychological tests. Independent component analysis and NH analysis were applied to analyze the imaging data. RESULTS: Relative to HCs, BipM patients displayed increased NH in the left middle frontal gyrus (MFG), and rBD patients displayed increased NH in the right inferior parietal lobule (IPL). Compared to rBD patients, BipM patients displayed reduced NH in the right IPL. Furthermore, support vector machine results exhibited that NH values in the right IPL could distinguish BipM patients from rBD patients with 69.70 %, 57.89 %, and 91.67 % for accuracy, sensitivity, and specificity, respectively, and support vector regression results exhibited a significant association between predicted and actual symptomatic improvement based on the reduction ratio of the Young` Mania Rating Scale total scores (r = 0.466, p < 0.01). CONCLUSION: The study demonstrated distinct NH values in the FPN could serve as a valuable neuroimaging biomarker capable of differentiating patients with BipM and rBD, and NH values of the left MFG as a potential predictor of early treatment response in patients with BipM.

Chronic inflammatory demyelinating polyneuropathy and psoriasis comorbidity with significantly alleviated in symptoms after secukinumab: case report.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that involves damage to the peripheral nervous system. The course of the disease can progress for more than 8 weeks, with frequent incidences of relapse-remission courses. This article reported a rare combination of CIDP with fluctuating symptoms, recurrence-remission, and comorbidity with psoriasis. CASE PRESENTATION: A 29-year-old male patient with repeated limb weakness and numbness was admitted to the hospital several times in the past six months. He had a history of psoriasis for 6 years, and the medications (clobetasol propionate ointment and calcipotriol ointment) treated for psoriasis were discontinued 1 year ago. During the hospitalization, repeated intravenous injections of human immunoglobulin G (IVIg), immunoadsorption, and secukinumab were performed. Nerve electrophysiology tests, ganglioside autoantibody spectrum tests, and clinical MRC muscle strength scores were performed on a regular basis to confirm the diagnosis of CIDP. The patient was regularly followed up. RESULTS: After repeated rounds of human IVIg and immunoadsorption, the patient's MRC score was increased by ≥ 6 points. The first ganglioside autoantibody spectrum test showed anti-GQ1b IgG ( +) and anti-GM1 IgM ( +) antibodies, and all were negative after re-examination. Finally, the patient was treated with the IL-17A inhibitor secukinumab for psoriasis. During 7 months of follow-up, the CIDP and psoriasis symptoms are relatively stable. CONCLUSION: Combination of IVIg and immunoadsorption was highly effective in treating CIDP complicated with psoriasis. The clinical manifestations of CIDP are diverse. When relapse-remission occurs in the course of the disease, it is necessary to clarify whether it is combined with other autoimmune diseases and should control the autoimmune diseases as soon as possible.

'Multiple and short-range' cross-linking of dialdehyde carboxymethyl cellulose contributes to regulating the physicochemical property of collagen fibril.

Collagen fibril hydrogel (CH), with controllable micro-structure, sufficient modifying sites and excellent biocompatibility, has received widely attention in the regulation of biomacromolecules. Herein, dialdehyde carboxymethyl cellulose (DCMC) in different -CHO contents and molecular weights demonstrated two types of cross-linking behaviors to CH, 'limited and long-range' or 'multiple and short range' cross-linking, corresponding to -CHO content ranged from 0 to 53 % and 53 to 90 %, respectively. In regard of structure, non-destroying effect of DCMC on collagen was supported by FT-IR and XRD analysis. CH cross-linked by DCMC (CH-DC) showed declining porosity and aggregating fibrils as -CHO content of DCMC rising. In regard of physicochemical properties, DCMC with >53 % -CHO strengthened the hydrophilicity, thermal stability and degradation resistance of CH-DC. Also, there was 110 % growth on gel strength, 86 Pa enhancements on storage modulus, and 4.6 times decrease on the swelling ratio of CH-DC. Results indicated that DCMC with 79 % -CHO remarkably improved the physicochemical properties of CH via developing sufficient Schiff-base bonds with collagen fibril in a short distance. This study distinguished two patterns of DCMC cross-linking from physicochemical view. In other words, DCMC is potential to meet the requirement of protein-based materials with different expectations by adjusting its -CHO content and molecular weight.

Ring finger sensory latency difference in the diagnosis and treatment of carpal tunnel syndrome.

OBJECTIVE: To explore the sensitivity of median and ulnar nerve sensory latency differences in diagnosing carpal tunnel syndrome (CTS) at different severities. METHODS: CTS patients were divided into three groups based on disease severity (mild, moderate, and severe). Distal latency of sensory nerve action potential (SNAP) for the median and ulnar nerves was recorded. The sensitivity of SNAP distal latency to CTS and its correlation with CTS severity were analyzed. RESULTS: Significant differences were found in the median nerve sensory action potential distal latency (MSDL) and in the median and ulnar sensory latency difference to ring finger (MUD) but not in the ulnar nerve sensory action potential distal latency (USDL) between CTS and control. The sensitivity and specificity were 92.2 and 99.4% with an MSDL cutoff value of 2.40 ms, respectively, and were both 100% with a MUD cutoff value of 0.33 ms. There was no significant difference in USDL among the CTS and control groups. Significant differences were found in MSDL and MUD among the CTS severities and between mild and moderate CTS, but not between mild and severe CTS or between moderate and severe CTS. Correlations with CTS severity were observed for MSDL and MUD but not for USDL. CONCLUSION: The ulnar nerve of the CTS patients was not damaged. A smaller MSDL reflected median nerve damage, which can be used for the early diagnosis of CTS. MUD correlated with CTS severity with a higher sensitivity than MSDL, which can provide therapeutic insight without pain to patients.

Overexpressed lncRNA ROR Promotes the Biological Characteristics of ox-LDL-Induced HUVECs via the let-7b-5p/HOXA1 Axis in Atherosclerosis.

The long non-coding RNA regulator of reprogramming (lncRNA ROR) is involved in atherosclerosis (AS), but the specific mechanism remains unclear. The expressions of lncRNA ROR, let-7b-5p, Homeobox A1 (HOXA1), and apoptosis-associated proteins in the serum of AS patients and human umbilical vein endothelial cells (HUVECs) were determined by quantitative real-time PCR (qRT-PCR) and Western blot. The relationships of lncRNA ROR, let-7b-5p, and HOXA1 were analyzed by Pearson's correlation test. The viability and the migration of HUVECs were measured by Cell Counting Kit-8, wound healing, and Transwell assays. The predicted target gene and the potential binding sites were confirmed by dual-luciferase reporter assay. lncRNA ROR was highly expressed in AS, which promoted the cell viability and migration of HUVECs, while lncRNA ROR silencing produced the opposite results. The expression of let-7b-5p, which bound to lncRNA ROR, was downregulated in AS, indicating that the two genes were negatively correlated. Besides this, let-7b-5p reversed the effects of upregulated lncRNA ROR expression on let-7b-5p expression, cell viability, and migration as well as the expressions of apoptosis-related proteins of ox-LDL-treated HUVECs. HOXA1 was targeted by let-7b-5p and upregulated in AS, with its expression being negatively correlated with let-7b-5p but positively correlated with lncRNA ROR. In ox-LDL-treated HUVECs, overexpressed HOXA1 reversed the effects of let-7b-5p, and HOXA1 silencing reversed the effects of lncRNA ROR. In AS, lncRNA ROR promoted the biological characteristics of oxidation of low-density lipoprotein-induced HUVECs via the let-7b-5p/HOXA1 axis.

Effect of Arylmethylene Substitutions on Molecular Structure, Optoelectronic Properties and Photovoltaic Performance of Dithienocyclopentafluorene-Based Small-Molecule Acceptors.

Two dithienocyclopentafluorene-based small-molecule acceptors (SMAs) were developed that feature methylene-functionalized conjugated side chains, to study the effect of arylmethylene substitution and its number on structure, optoelectronic properties and device performance. Results showed that two SMAs have better absorption properties and planarity, lower bandgaps and higher LUMOs compared with the control SMA without conjugated side chains. The synthesized SMAs were tested in polymer solar cells for examples of their applicability. This work argues that the introduction of methylene-functionalized conjugated side chains has great potential in tuning molecular structure, optoelectronic properties, device physics and photovoltaic performance of SMAs.

Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance.

The use of immune checkpoint inhibitors (ICI) in treating cancer has revolutionized the approach to eradicate cancer cells by reactivating immune responses. However, only a subset of patients benefits from this treatment; the majority remains unresponsive or develops resistance to ICI therapy. Increasing evidence suggests that metabolic machinery in the tumor microenvironment (TME) plays a role in the development of ICI resistance. Within the TME, nutrients and oxygen are scarce, forcing immune cells to undergo metabolic reprogramming to adapt to harsh conditions. Cancer-induced metabolic deregulation in immune cells can attenuate their anti-cancer properties, but can also increase their immunosuppressive properties. Therefore, targeting metabolic pathways of immune cells in the TME may strengthen the efficacy of ICIs and prevent ICI resistance. In this review, we discuss the interactions of immune cells and metabolic alterations in the TME. We also discuss current therapies targeting cellular metabolism in combination with ICIs for the treatment of cancer, and provide possible mechanisms behind the cellular metabolic rewiring that may improve clinical outcomes.

Cationic Polyelectrolytes with Alkylsulfonate Counterions as a Cathode Interface Layer for High-Performance Polymer Solar Cells.

Three cationic polyelectrolytes polyethyleneimine ethoxylate (PEIE)-1,4-butanediol dimethylsulfonate (MSB), PEIE-1,4-butanediol diethylsulfonate (ESB), and PEIE-1,4-butanediol dibenzylsulfonate (BSB), containing methylsulfonate, ethylsulfonate, and benzylsulfonate, respectively, were prepared for cathode interface layers (CILs) via a one-step reaction with 1,4-butanediol dialkylsulfonate and PEIE as the reactants. The results indicate that PEIE-MSB and PEIE-ESB with smaller counterions possess more efficient electron extraction, higher electron mobilities, and better photovoltaic performance than PEIE-BSB with larger counterions. The PTB7-Th:PC71BM-based single junction bulk heterojunction polymer solar cells (PSCs) with PEIE-ESB as the CIL showed power conversion efficiencies (PCEs) of 10.44 and 9.23% under the thickness conditions of 8 and 30 nm, respectively. The PM6:Y6-based PSCs displayed a high PCE of 15.69%. The study provides not only new high-performance CILs but also a new strategy to construct light-soaking-free PSCs via tuning alkylsulfonate counterions.

High Incidence of Axillary Web Syndrome among Breast Cancer Survivors after Breast Reconstruction.

OBJECTIVE: The aim of this study was to identify if breast reconstruction is a surgical risk factor for axillary web syndrome (AWS) in breast cancer (BC) patients. METHODS: The data of 207 patients who have been diagnosed with unilateral BC and who had mastectomy and lymph node dissection were retrospectively reviewed. Information of their clinical and pathological data, whether they had immediate -reconstruction and intraoperative radiotherapy, surgical methods, and postoperative complications during the 3 months after their surgery (AWS, lymphedema, seroma, and myofascial adhesion) were collected, and the incidence of AWS was compared between different surgical methods. RESULTS: The overall incidence of AWS was 48.8% in 207 patients. Of the 22 patients who received reconstruction, 19 developed AWS, yielding an incidence of 86%. Multivariate logistic regression modeling showed that patients who underwent reconstruction had a significantly higher incidence of AWS (odds ratio, 4.74), as did patients with postoperative complication of myofascial adhesion (odds ratio, 7.07). CONCLUSIONS: BC survivors after breast reconstruction are susceptible to AWS, and there is a significant association between myofascial adhesion and AWS. Our results can stimulate further investigation and provide an evidence base for the development of educational guidance for patients who plan to undergo breast reconstruction.

ß-Arrestin 2 protects against neurological function defects in HSV-1-induced encephalitis mice.

The pathogenesis of herpes simplex encephalitis (HSE) needs to be fully explored. ß-Arrestin 2 (Arrb2) is highly expressed in brain tissues and plays a key role in the regulation of systemic immune reactions by modulating various signaling pathways. However, the expression of Arrb2 in microglial cells and its influence on HSE prognosis is still undefined. We explore the pathophysiological effect of Arrb2 in the brain using experimental HSE mice. The expression of Arrb2 in microglia was decreased significantly 48 hours following HSV-1 infection. Arrb2 overexpression transgenic (TG) mice had a significantly lower mortality and survival rate was improved by 40% compared to wild-type mice. Arrb2 suppressed the generation of proinflammatory cytokines TNF-α and IL-6 and increased anti-inflammatory cytokines IL-10 and IL-4 expression. Arrb2 also inhibited the activation of the transcription factor NF-κB in microglial cells. Arrb2 TG mice attenuated the blood-brain barrier breakdown and relieved cerebral edema, meanwhile, Arrb2 improved mice neurological function compared with wild-type mice. Overall, Arrb2 favored microglia of the M2 phenotype, attenuated brain proinflammatory responses, protected the blood vessel wall integrity, reduced HSV-1-induced neurological impairment, and improved the survival rate in HSE mice.

Nonhalogenated-Solvent-Processed Efficient Polymer Solar Cells Enabled by Medium-Band-Gap A-π-D-π-A Small-Molecule Acceptors Based on a 6,12-Dihydro-diindolo[1,2-b:10,20-e]pyrazine Unit.

In this contribution, a series of A-π-D-π-A small molecules (SMs), IPY-T-IC, IPY-T-ICCl, and IPY-T-ICF, containing the central donor unit (D) of 6,12-dihydro-diindolo[1,2-b:10,20-e]pyrazine (IPY), the π-conjugated bridge of thiophene, and the end-accepting group (A) of 3-(dic yanomethylidene)indol-1-one, 5,6-dichloro-3-(dicyanomethylidene)indol-1-one, or 5,6-difluoro-3-(dicyanomethylene)indol-1-one, were developed, characterized, and employed as the acceptor materials for polymer solar cells (PSCs). Influences of the different end-accepting groups on thermal properties, spectral absorption, energy levels, photovoltaic performance, and film morphology of these small-molecule acceptors (SMAs) were investigated in detail. These SMAs exhibit an excellent thermal stability and strong crystallization. The absorption spectra of these SMs mainly locate the wavelength between 400 and 700 nm, associated with the optical band gaps in the range of 1.75-1.90 eV. Compared with nonhalogenated IPY-T-IC, the halogenated SMAs IPY-T-ICCl and IPY-T-ICF present better absorption abilities, wider absorption region, and downshifted highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) levels. With regard to the complementary spectral absorption and matched HOMO/LUMO levels, PTB7-Th as a low-band gap polymer was chosen to be an electron donor to pair with these SMAs for fabricating bulk-heterojuntion PSCs. Under optimized conditions, among these SMAs, the PTB7-Th:IPY-T-IC-based PSC processed from a halogenated solvent system (chlorobenzene + 1-chloronaphthalene) delivers the best power conversion efficiency (PCE) of 7.32%, mainly because of more complementary spectral absorption, upper-lying LUMO level, higher and balanced carrier mobility, more efficiently suppressed trap-assisted recombination, better charge collection property, and blend morphology. Encouragingly, an improved PCE of up to 7.68% is achieved when the IPY-T-IC-based solar cell was processed from a nonhalogenated solvent system (o-xylene + 2-methylnaphthalene). In view of the large band gap of these IPY-based SMAs, the PCE of over 7.5% is notable and attractive for the related community. Our study argues that the IPY moiety is a potential electron-donating building moiety to develop medium-band-gap high-performance A-π-D-π-A SMAs for nonhalogenated-solvent-processed photovoltaic devices.

A triple signal amplification method for chemiluminescent detection of the cancer marker microRNA-21.

Mesoporous silica nanospheres (MSNs) are used in a triple signal amplification chemiluminescent (CL) assay for microRNA-21. It is based on (a) the synergistic amplification via loading and controlled-release of signal reagents by MSNs, (b) target recycling amplification, and (c) the enhancement effect of graphene oxide quantum dots (GOQD). CL is generated by the bis(2,4,6-trichlorophenyl) oxalate (TCPO) and H2O2 reaction in the presence of the fluorophore rhodamine B (RB). RB is firstly loaded into the pores of MSNs modified with amino groupsand coupled with ssDNA. Then, the pores are capped by GOQD. Upon the addition of microRNA-21 into the system, the designed ssDNA assumes a double stranded structure. With the aid of duplex-specific nuclease, the double strand structure is cleaved and the free microRNA-21 enters into the next cycling process to combine with other ssDNA forming double strand structures. After several cycling process, amounts of GOQDs departing from the surface of MSNs cause the opening of the pores of MSNs and the release of RB causes the CL of TCPO-H2O2 reaction system. Free GOQDs can lead to a further CL enhancement. By this method, even a low amount of microRNA-21 leads to a large number of released RB molecules and triggers high-intensity CL. The method was applied in an assay where the CL signal increases linearly with the logarithm of the microRNA-21 concentration in the range of 0.005-50 pmol L-1 and the detection limit is 1.7 fmol L-1 (at 3σ). Graphical abstract Schematic presentation of a triple signal amplification chemiluminescence (CL) analysis platform based on rodamine B (RB) loading and controlled release, target recycling amplification and graphene oxide quantum dots (GOQD) as the enhancer for analysis of microRNA-21 in human serum.

Screening Gene Mutations in Chinese Patients With Benign Essential Blepharospasm.

Objective: This study aimed to screen gene mutations in Chinese patients with benign essential blepharospasm (BEB) to understand its etiology. Methods: Twenty BEB patients diagnosed by clinical manifestations between April 2015 and October 2015 were enrolled. All the cases were investigated by questionnaires about general conditions, social behavioral factors, environmental factors, psychological factors, genetic factors, and previous diseases. In each patient, a total of 151 genes related to movement disorders were analyzed by second-generation sequencing. Results: Two patients had a family history of BEB, and they had SYNE1 and Cdkn1A-interacting zinc finger protein 1 (CIZ1) mutation, respectively. We found the SYNE1 mutation in seven patients, the CIZ1 mutation in two patients, the CACNA1A mutation in two patients, the LRRK2 mutation in two patients, and the FUS mutation in two patients. The C10orf2, TPP1, SLC1A3, PNKD, EIF4G1, SETX, PRRT2, SPTBN2, and TTBK2 mutations were found in only one patient, respectively, while not any mutation in the 151 genes were found in two patients. Some patients had mutations in two genes. Conclusion: Genetic factors, especially SYNE1 and CIZ1 mutations, contribute to the etiology of BEB.

Human Cytomegalovirus Productively Replicates In Vitro in Undifferentiated Oral Epithelial Cells.

Human cytomegalovirus (HCMV) productive replication in vitro is most often studied in fibroblasts. In vivo, fibroblasts amplify viral titers, but transmission and pathogenesis require the infection of other cell types, most notably epithelial cells. In vitro, the study of HCMV infection of epithelial cells has been almost exclusively restricted to ocular epithelial cells. Here we present oral epithelial cells with relevance for viral interhost transmission as an in vitro model system to study HCMV infection. We discovered that HCMV productively replicates in normal oral keratinocytes (NOKs) and telomerase-immortalized gingival cells (hGETs). Our work introduces oral epithelial cells for the study of HCMV productive infection, drug screening, and vaccine development.IMPORTANCE The ocular epithelial cells currently used to study HCMV infections in vitro have historical significance based upon their role in retinitis, an HCMV disease most often seen in AIDS patients. However, with the successful implementation of highly active antiretroviral therapy (HAART) regimens, the incidence of HCMV retinitis has rapidly declined, and therefore, the relevance of studying ocular epithelial cell HCMV infection has decreased as well. Our introduction here of oral epithelial cells provides two alternative in vitro models for the study of HCMV infection that complement and extend the physiologic relevance of the ocular system currently in use.