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Augmented CD4 + T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4 + T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4 + T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4 + T cell subsets in vitro, and mice with KAT6A-deficient CD4 + T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4 + T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical and neuroelectrophysiological characteristics of patients with primary peripheral nerve hyperexcitability syndrome (PNHS). Methods: The clinical data of 20 patients who were diagnosed with PNHS in Beijing Tiantan Hospital from April 2016 to January 2023 were retrospectively collected. All patients underwent neuroelectrophysiological examinations. Clinical and electrophysiological characteristics were compared between the antibody positive and antibody negative groups, according to serum and cerebrospinal fluid anti-contactin-associated protein-like 2 (CASPR2) and/or anti-leucine-rich glioma-inactivated protein 1 (LGI-1) antibodies. Results: There were 12 males and 8 females, with a mean age of (44.0±17.2) years and the disease course of [ M ( Q 1 , Q 3 )] 2.3 (1.1, 11.5) months. Motor symptoms included fasciculations, myokymia, muscle pain, cramps, and stiffness. These symptoms were commonly seen in the lower limbs (17 patients), followed by upper limbs (11 patients), face (11 patients) and trunk (9 patients). Nineteen (19/20) patients had sensory abnormalities and/or autonomic dysfunction, 13 patients had central nervous system involvement, and 5 patients had concomitant lung cancer or thymic lesions. The characteristic spontaneous potentials on needle electromyography (EMG) were myokymia potential (19 patients), fasciculation potential (12 patients), spastic potential (3 patients), neuromyotonic potential (1 patients), etc, which were commonly seen in the lower limb muscles, especially the gastrocnemius muscle(12 patients). After-discharge potential was found in 8 patients, and 7 were in the tibial nerve. Seven patients had positive serum anti-CASPR2 antibodies, and 3 of them had concomitant anti-LGI1 antibodies. And 1 patient had positive serum anti-LGI1 antibody alone. Compared with patients in the antibody negative group ( n =12), the patients who had anti-VGKC complex antibodies ( n =8) had a shorter course of disease [ M ( Q 1 , Q 3 ): 1.8 (1, 2) months vs 9.5 (3.3, 20.3) months, P =0.012], higher incidence of after-discharge potential (6/8 vs 2/12, P =0.019). The immunotherapy regimen (multi-dru, single-drug, no immunotherapy: 6, 2, 0 patients) in antibody-positive patients was different from the antibody-negative group (3, 6, 3 patients, U =21.00, P =0.023). Conclusions: The symptoms of motor nerve hyperexcitation, characteristic EMG spontaneous potentials and after-discharge potentials in PNHS patients are most commonly seen in the lower limbs. Attention should be paid to concomitant sensory and autonomic nerve hyperexcitation. PNHS patients with positive serum anti-CASPR2 antibodies may require immunotherapy with multiple drugs.

This article reported the clinical experience of diagnosis and treatment for two patients with lymphomatosis cerebri. Case 1 was female and aged 53 years old, while case 2 was male and aged 69 years old. Progressive cognitive impairment was the main clinical manifestation in both patients. Brain magnetic resonance imaging (MRI) suggested leukoencephalopathy with patchy or mass enhancement. Cerebral blood flow was reduced on perfusion imaging in one patient. Brain biopsy confirmed diffuse large B-cell lymphoma in both cases. The concentration of interleukin-10 in cerebrospinal fluid (CSF) of two patients was significantly increased, however, the result of CSF flow cytology was negative. The current study suggests that interleukin-10 in CSF is an important biological indicator for the diagnosis of lymphomatosis cerebri, but CSF flow cytometry may not be helpful. Moreover, cerebral hypoperfusion can be present in patients with lymphomatosis cerebri.

Background: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL., Methods: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated., Results: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs., Conclusion: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Thermodynamically induced tensile stress in the perovskite film will lead to the formation of atomic vacancies, seriously destroying the photovoltaic efficiency stability of the perovskite solar cells (PSCs). Among them, cations and halide anions vacancies are unavoidable; these point vacancies are considered to be a major source of the ionic migration and perovskite degradation at the crystal boundary and surface of the perovskite films. Here, we use choline bromide to modify the perovskite film by occupying the atomic defects in the CsPbBr 3 perovskite film. The results show that the zwitterion quaternary ammonium ions and bromide ions in choline bromide can simultaneously occupy the Cs + cation and Br - anions vacancies in the perovskite film by the ionic bonding effect, for which the defect-state density on the surface of the perovskite film can be significantly reduced, leading to the effective enhancement of carrier lifetime. In addition, the residual stress at the crystal boundary can be effectively reduced by lowering the Young's modulus in the CsPbBr 3 perovskite film. As a result, the optimized device achieves a photoelectric conversion efficiency (PCE) of 9.06% with an increase of 41.1% compared to the control device with a PCE of 6.42%. Most importantly, the newborn thermal stress due to thermal expansion during heat working conditions can be transferred from the polycrystalline perovskite to the carbon layer by the matched Young's modulus, thus resulting in improved stability perovskite film under environmental conditions. The work provides new insights for preparing high-quality perovskite films with low defect-state density and residual stress.

A diastereoselective α-sulfenylation of chiral α-aryl/alkyl N- tert-butanesulfinyl imidates has been developed. Suitable sulfur electrophiles can be used as sulfenylating reagents to intercept aza-enolates generated from imidate deprotonation, giving α-thiofunctionalized imidates in good yields with high diastereocontrol. This protocol for C-S bond formation can efficiently synthesize enantioenriched 1,2-sulfanyl amine derivatives such as sulconazole.

The objective of this study was to examine the clinical findings, magnetic resonance imaging (MRI), pathological features, and treatment experiments of patients with hypertrophic cranial pachymeningitis (HCP). The clinical findings, MRI, and pathological appearances of 9 patients with HCP were analyzed retrospectively. The thickened dura mater was markedly enhanced after contrast media injection. The lesion near the brain hemisphere presented long regions of T1- and T2-weighted abnormal signal intensities. The abnormal signal intensities of the brain tissue were decreased significantly. Pathological examination demonstrated chronic inflammation changes, with cerebral dura mater fibrous tissue showing obvious hyperplasia, and the periphery of the blood vessel showing a great quantity of infiltrating phlegmonosis cells. HCP mainly presents headache and paralysis of multiple cranial nerves. The distinctive signs on brain MRIs involve strengthening the signal in the cerebral dura.

Objective: The aim of this study was to perform perfusion CT imaging in the acute phase of myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), to assess whether these patients had cerebral perfusion abnormalities. Furthermore, the pathology of muscle vessel was evaluated, to explore the role of vasculopathy and ischemic events in the pathogenesis of mitochondrial encephalomyopathies., Methods: Computed tomography perfusion (CTP) imaging was applied to the evaluation of brain perfusion during the symptomatic period of mitochondrial encephalomyopathies. Mitochondria structures in the blood vessels wall within muscle fibers were observed by light and electron microscopy analyses., Results: Neuroimaging studies demonstrated uni- and bilateral lesions predominantly in the occipital and temporal-parietal lobes. Compared with the healthy control subjects, significant decreases in cerebral blood flow and cerebral blood volume were noted in affected brain areas of individuals with MELAS. In particular, mean transit time and the time to peak were prolonged both in lesion and non-lesion brain areas. Muscle pathology showed large granular deposits on vessel wall as demonstrated by succinic acid dehydrogenase staining. Electron microscopy of blood vessels revealed swelling of cristae and a striking increase in the number of mitochondria in the smooth muscle and endothelial cells., Conclusion: Insufficient cerebral perfusion or vascular reserve and secondary metabolic dysfunction may represent an important feature of the pathogenesis of the stroke-like episodes in MELAS.

Objective: To investigate the ultrastructural features of mitochondrial cytopathies and its diagnostic value., Methods: Muscle biopsy specimens from 33 cases of mitochondrial cytopathies were examined by routine pathological and electron microscopic examinations., Results: The main pathologic changes included ragged red fibers in modified Gomori staining, hyper-intense staining myofibers in SDH, COX-negative fibers while dark counterstaining with SDH in COX/SDH double staining technique. Ultrastructural findings included subsarcolemmal and intramyofibrillar proliferation of mitochondria and the appearance of abnormal mitochondria, paracrystalline inclusions, concentric dystrophic cristae and excessive subsarcolemmal glycolipid compounds in subsarcolemmal., Conclusion: The presence of proliferation and abnormality of mitochondria, electro-dense granule and paracrystalline inclusions in mitochondria provide key diagnostic evidence for the diagnosis of this disease.

Objective: To analyze the impact of hematoma location and vascular territory on the clinical symptoms and signs, neuroimaging findings, and clinical prognosis of striatocapsular hemorrhage., Methods: The data of 181 cases of striatocapsular hemorrhage, 124 males and 57 females, aged 28 - 89, including medical history, symptoms, and signs were analyzed. On the basis of hematoma locations and arterial territories, the striatocapsular hemorrhage was divided into six types: anterior type (with the blood supply from Heubner's artery), middle type (with the blood supply from medial lenticulostriate artery), posteromedial type (with the blood supply from anterior choroidal artery), posterolateral type (with the blood supply from posteromedial branches of lateral lenticulostriate artery), lateral type (with the blood supply from the most of lateral branches of lenticulostriate artery), and massive type (with the hematoma occupying the whole or greater part of striatocapsular region). The short-term clinical outcome and prognosis were evaluated by Modified Rankin Scale (MRS). The relationship between the type and outcome was analyzed., Results: There were 22 cases of anterior type, accounting for 12.15%, of which 68.18% showed an excellent outcome (MRS = 0 - 2) and only 1 case died. There were 12 cases of middle type, accounting for 6.63%, of which 6 cases (50%) showed a poor outcome (MRS = 5) but without dead case. There were 19 cases of posteromedial type (10.50%), of which 52.63% had excellent outcome (MRS = 0 - 2) without dead case. There were 19 cases of posterolateral type (18.78%), of which 76.47% were with poor outcome (MRS = 5) and 17.65% died. Accounting for 39.23%, lateral type was the most common condition, of which 38.03% patients had a poor outcome (MRS = 5) and 8.45% cases died. The incidence rate of massive type was also high (12.71%), of which 47.82% showed a poor outcome (MRS = 5) and 47.83% cases died., Conclusion: Hematoma location and vascular territory are the determinating factors of prognosis of striatocapsular hemorrhage. The six-type classification system provides a simple and reliable means to predict the clinical outcomes and to guide therapeutic options of striatocapsular hemorrhage.