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ABSTRACTBackground Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials.Research design and methods Study-1 involved subjects were randomized (1:1:1) to receive 20 μg ReCOV, 40 μg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 μg ReCOV (pilot batch, ReCOV HA), 20 μg ReCOV (commercial batch, ReCOV TC), or 30 μg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster.Results Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence.Conclusions Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV’s potential for enhanced protection, supported by strong cross-neutralization and immune persistence.Clinical Trial Registration Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Abstract We propose two approaches for extracting the total gluon helicity contribution to proton spin from lattice QCD, one from local operator matrix elements in a fixed gauge accessible on lattice with feasible renormalization, and the other from gauge-invariant nonlocal gluon correlators. Neither of these approaches requires a matching procedure when converted to the MS ¯ $$ \overline{\textrm{MS}} $$ scheme. Our proposal resolves a long-standing inconsistency in the literature regarding lattice calculations of the total gluon helicity, and has the potential to greatly facilitate these calculations.

Abstract Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Abstract 2,5-Dimethylpyrazine (2,5-DMP) is important pharmaceutical raw material and food flavoring agent. Recently, engineering microbes to produce 2,5-DMP has become an attractive alternative to chemical synthesis approach. In this study, metabolic engineering strategies were used to optimize the modified Escherichia coli BL21 (DE3) strain for efficient synthesis of 2,5-DMP using L-threonine dehydrogenase (EcTDH) from Escherichia coli BL21, NADH oxidase (EhNOX) from Enterococcus hirae, aminoacetone oxidase (ScAAO) from Streptococcus cristatus and L-threonine transporter protein (EcSstT) from Escherichia coli BL21, respectively. We further optimized the reaction conditions for synthesizing 2,5-DMP. In optimized conditions, the modified strain can convert L-threonine to obtain 2,5-DMP with a yield of 2897.30 mg/L. Therefore, the strategies used in this study contribute to the development of high-level cell factories for 2,5-DMP. Graphical Abstract

BackgroundAlport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed COL4A5 gene alterations.MethodsThree Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals’ peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members.ResultsBoth probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative α3 and α5 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A’s mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C>T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene COL4A5 (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects.ConclusionThe novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the COL4A5 gene but also indicate that carriers of both mutation sites and those with mutation c.5020C>T may present NS as their primary clinical manifestation.

IntroductionWe previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models.MethodsATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson’s disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish.ResultsCells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson’s disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio.ConclusionThis study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

Wasp venom injections from wasp stings can damage several organs, most commonly the kidneys. Despite literature evidence, wasp sting-induced acute kidney injury (AKI) is rare and involves complex pathophysiological processes. While acute tubular necrosis (ATN) is the most prevalent histological result of wasp sting-induced AKI, uncommon combinations of chronic renal lesions have been described, alerting us to the patient's underlying illness. We report a 55-year-old hypertensive patient with unknown renal function who got AKI following multiple wasp stings. His renal function had not improved after continuous hemodialysis and plasma exchange; therefore, a kidney biopsy was performed. The pathology revealed that in addition to ATN, his kidney's distinguishing feature was a mix of chronic interstitial renal disease and chronic glomerulosclerosis. We think that his current renal pathological results were caused by hypertension in addition to wasp venom.

Abstract We present a unified framework for the perturbative factorization connecting Euclidean correlations to light-cone correlations. Starting from nonlocal quark and gluon bilinear correlators, we derive the relevant hard-matching kernel up to the next-to-leading-order, both for the flavor singlet and non-singlet combinations, in non-forward and forward kinematics, and in coordinate and momentum space. The results for the generalized distribution functions (GPDs), parton distribution functions (PDFs), and distribution amplitudes (DAs) are obtained by choosing appropriate kinematics. The renormalization and matching are done in a state-of-the-art scheme. We also clarify some issues raised on the perturbative matching of GPDs in the literature. Our results provide a complete manual for extracting all leading-twist GPDs, PDFs as well as DAs from lattice simulations of Euclidean correlations in a state-of-the-art strategy, either in coordinate or in momentum space factorization approach.

BackgroundDouble inferior vena cava (DIVC) is a rare vascular malformation. With advances in radiological techniques and diagnosis, more and more types of DIVC were identified and diagnosed. Recognition of the variety of DIVC seen on imaging is essential for subsequent venous interventions.Case presentationA 77-year-old man presented with low back pain with left lower limb pain for 1 month. Scattered petechiae above the skin surface on the left lower leg, especially on the extensor surface, with flaking and mild tingling of the skin, were noted 3 weeks ago. Ultrasound revealed deep vein thrombosis (DVT) in the left lower limb. Computed tomography pulmonary angiography (CTPA) suggested no significant thrombus in the pulmonary artery. Computed tomography venography (CTV) of bilateral lower limbs showed that iliac vein compression syndrome with formation of deep and superficial venous traffic branches in bilateral lower limbs, predominantly on the left side. CTV of the inferior vena cava (IVC) suggested that the left common iliac vein crossed the common iliac artery bifurcation from dorsal to ventral and continued to travel cranially as a ventral vessel, and connected with the ventral IVC anterior to the right common iliac artery. The right common iliac vein extended cephalad as a dorsal vessel, which was narrowed at the level of 4th lumbar vertebra by compression of the hyperplastic bone and the osteophyte. The patient was discharged after right and left common iliac vein angiography and balloon dilation of bilateral common iliac vein.ConclusionThe formation of both ventrally and dorsally aligned DIVC is rarer. It should be clarified the effects of DIVC on DVT formation, and the importance of imaging for preoperative planning.

Abstract We demonstrate that gluon transverse-momentum-dependent parton distribution functions (TMDPDFs) can be extracted from lattice calculations of appropriate Euclidean correlations in large-momentum effective theory (LaMET). Based on perturbative calculations of gluon unpolarized and helicity TMDPDFs, we present a matching formula connecting them and their LaMET counterparts, where the latter are renormalized in a scheme facilitating lattice calculations and converted to the MS ¯ $$ \overline{\textrm{MS}} $$ scheme. The hard matching kernel is given up to one-loop level. We also show that the perturbative result is independent of the prescription used for the pinch-pole singularity in the relevant correlations. Our results offer a guidance for the extraction of gluon TMDPDFs from lattice simulations, and have the potential to greatly facilitate perturbative calculations of the hard matching kernel.

In the large-momentum expansion for parton distribution functions (PDFs), the natural physics scale is the longitudinal momentum (pz) of the quarks (or gluons) in a large-momentum hadron. We show how to expose this scale dependence through resumming logarithms of the type lnn⁡pz/μ in the matching coefficient, where μ is a fixed renormalization scale. The result enhances the accuracy of the expansion at moderate pz>1 GeV, and at the same time, clearly shows that the partons cannot be approximated from quarks with pz∼ΛQCD which are not predominantly collinear with the parent hadron momentum, consistent with power counting of the large-momentum effective theory. The same physics mechanism constrains the coordinate space expansion at large distances z, the conjugate of pz, as illustrated in the example of fitting the moments of the PDFs.

BackgroundDevelopment of endovascular interventional techniques gradually replaced traditional open surgery and has become the preferred treatment for renal aneurysms. This study aimed to analyze the clinical characteristics of renal artery aneurysm (RAA) and the safety and efficacy of intravascular interventional treatment.Materials and MethodsWe retrospectively analyzed the clinical characteristics and imaging data of 23 aneurysms in 18 patients with RAA. The technical success rate, complication rate, mortality rate, reintervention rate, and use of embolization materials were evaluated.ResultsIn 18 patients with RAA (age, 32–72 years, average age, 52.2 ± 11.2 years), a total of 23 aneurysms were found (diameter 0.5–5.5 cm, average diameter 2.2 ± 1.4 cm). Among them, 11 cases (61.1%) were discovered accidentally, and the remaining patients were diagnosed due to the following major complaints: four cases (22.2%) presented low back pain, two (11.1%) were due to high blood pressure, and one (5.5%) had low back pain with gross hematuria. A total of 14 aneurysms in 13 patients received endovascular interventional therapy. The technical success rate of 13 patients with renal aneurysms was 100%. Three of the 18 patients were lost to follow-up, and the remaining were followed up for 4–89 months. There was no recurrence of the aneurysm or displacement of the stent or coil.ConclusionEndovascular treatment for RAA has a high success rate, low complication rate, and low reintervention rate. It has the advantage of less trauma and is flexible and more targeted for different types of renal aneurysms.

Abstract Background Protein S deficiency (PSD) is an autosomal dominant hereditary disease. In 1984, familial PSD was reported to be prone to recurrent thrombosis. Follow-up studies have shown that heterozygous protein S (PROS1) mutations increase the risk of thrombosis. More than 300 PROS1 mutations have been identified; among them, only a small number of mutations have been reported its possible mechanism to reduce plasma protein S (PS) levels. However, whether PROS1 mutations affect protein structure and why it can induce PSD remains unknown. Methods The clinical phenotypes of the members of a family with thrombosis were collected. Their PS activity was measured using the coagulation method, whereas their protein C and antithrombin III activities were measured using methods such as the chromogenic substrate method. The proband and her parents were screened for the responsible mutation using second-generation whole exon sequencing, and the members of the family were verified for suspected mutations using Sanger sequencing. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to detect the mRNA and protein expression of PROS1. Results In this family, the proband with venous thrombosis of both lower extremities, the proband’s mother with pulmonary embolism and venous thrombosis of both lower extremities, and the proband’s younger brother had significantly lower PS activity and carried a PROS1 c. 1820 T > C:p.Leu607Ser heterozygous mutation (NM_000313.3). However, no such mutations were found in family members with normal PS activity. The PS expression in the cell lysate and supernatant of the Leu607Ser mutant cells decreased, while mRNA expression increased. Immunofluorescence localization showed that there was no significant difference in protein localization before and after mutation. Conclusions The analysis of family phenotype, gene association, and cell function tests suggest that the PROS1 Leu607Ser heterozygous mutation may be a pathogenic mutation. Serine substitution causes structural instability of the entire protein. These data indicate that impaired PS translation and synthesis or possible secretion impairment is the main pathogenesis of this family with hereditary PSD and thrombophilia.

BackgroundBehçet’s disease (BD) is a unique autoimmune chronic systemic vasculitis that affects veins and arteries of all sizes. BD can lead to recurrent vascular events, especially venous thrombosis, with an incidence rate of 40%, or pseudoaneurysms formed under long-term inflammatory reaction or iatrogenic stimulation. BD-related risk factors promote endothelial dysfunction, platelet activation and overactivation of tissue factors leading to mural inflammatory thrombi. Thrombosis may be the first clinical manifestation of BD.Case presentationA 32-year-old man complaining of progressive swelling and pain in the right lower extremity for 30 days was initially diagnosed with “venous thrombosis of the right lower extremity,” using color Doppler ultrasonography. Patient underwent inferior vena cava filter placement combined with deep vein angioplasty of the right lower extremity and catheter-directed urokinase thrombolysis. Postoperative oral anticoagulant therapy was administered. However, the patient was readmitted 20 days later for pulsatile pain in the right groin. Prior medical history included 4 years of repeated oral and perineal ulcers, and 2 months of blurred vision. Abdominal computed tomography angiography (CTA) revealed rupture of the right common iliac artery (CIA) and left internal iliac artery (IIA), complicated by a pseudoaneurysm. Based on the clinical manifestations and other auxiliary examination results, the patient was re-diagnosed with “BD combined with deep venous thrombosis of the right lower extremity and an iliac artery pseudoaneurysm.” Stent implantation was performed for iliac artery pseudoaneurysm after symptoms were controlled with timely immunosuppressive therapy. After endovascular treatment, the patient underwent continued immunosuppressive therapy and dynamic reexaminations of abdominal CTA, which revealed that a small amount of contrast agent at the stent in the right CIA continued to flow into the cavity of the pseudoaneurysm; in addition, the size of the pseudoaneurysm was gradually increasing. Therefore, the patient underwent a second stent implantation for iliac artery pseudoaneurysm, and the condition improved further.ConclusionThe importance of early diagnosis of BD should be recognized, and the choice of interventional and surgical procedures should be carefully evaluated, as this may trigger further damage to vascular access in BD patients with aneurysm.

Dynamic mesh atomizers have been widely used in various fields because of their compact structure, low energy consumption, and low production costs. The finite element method is an important technique to analyze the factors affecting the atomization performance of dynamic mesh atomizers. However, at present, there is a lack of decisive solutions to the basic problems of boundary setting in terms of the simulation and vibration displacement characteristics of atomizers under different vibration modes. In this paper, two errors were found in the Vibration Analysis of a Piezoelectric Ultrasonic Atomizer to Control Atomization Rate paper written by Esteban Guerra-Bravo et al. in 2021. First, in the finite element analysis, the boundary condition of the atomizing sheet was set to be fixed, which is inconsistent with the actual support situation and seriously affects the vibration of the atomizing sheet. Second, in the simulation result, from the first mode to the third mode, the growth rate of the maximum displacement at the center of the atomizing sheet was as high as 77.12%, even up to 221.05%, which is inconsistent with the existing vibration theory. In view of these errors, in this paper, the working principle of dynamic mesh atomizers is analyzed and the vibration equation of the atomizing sheet under peripheral simple support is derived. Through comparison with the literature, it was proven that the boundary setting and vibration displacement of the atomizing sheet in the original paper are unreasonable. By measuring the atomizing rate of the atomizing sheet under different boundary conditions, it was proven that the peripheral freedom of the atomizing sheet should be greater than or equal to 1, namely, peripheral freedom or peripheral simply supported. The vibration displacement theory was used for the simulation, and the relationship between the vibration displacement and resonant frequency of the atomizing sheet under peripheral simple support was measured. It was found that with the increase in the resonance frequency, the maximum displacement of vibration modes with only nodal circles was larger than that of the other vibration modes, and the maximum displacement increased slightly with the increase in the number of nodal circles by about 0.98%.

Extraskeletal osteosarcoma is a rare malignant soft-tissue sarcoma that is difficult to diagnose. Surgery is a common treatment, although chemotherapy and radiotherapy are also used. Patients at risk of bleeding can undergo embolization combined with resection. The occurrence of primary splenic extraskeletal osteosarcoma in humans does not seem to have been reported in the literature. A 50-year-old woman who complained of pain in the left upper abdomen for 1 day was initially diagnosed with “splenic hemangioma with a high possibility of rupture and bleeding” and urgently underwent digital subtraction angiography, combined with splenic arteriography and embolization. Abdominal pain worsened 2 days postoperatively, with a hemoglobin level of 106.0 g/L. Consequently, emergency laparotomy combined with splenectomy was performed. The clinical and imaging features, pathological diagnosis, and embolization treatment of this case were analyzed retrospectively. CT of the upper abdomen revealed splenomegaly, an irregular low-density shadow in the spleen, and a flake-like calcification in the lateral margin of the left kidney. Nuclear MRI of the upper abdomen showed splenomegaly and a mass (approximately 8.4 cm × 5.7 cm × 6.3 cm) below the spleen with clear boundaries—this exhibited an uneven signal, which was slightly low in T1-weighted imaging (T1WI) and slightly high in T2-weighted imaging (T2WI). Several small cystic lesions or cystic cavities were observed in the mass, which exhibited a longer T2 signal. During the enhanced scan, the signal of the lesion showed progressive enhancement, and the enhancement range increased in the delayed phase scan, as well as a hematoma below the spleen capsule and calcification below the lesion (nodular T1WI/T2WI hypointense, approximately 3.3 cm × 3.6 cm). Postoperative biopsy pathology showed splenic soft tissue tumor: at low magnification, the multinucleated giant cells were scattered; at medium magnification, osteoclast-like multinucleated giant cells were observed; and at high magnification, lace- or grid-like tumor osteogenesis was detected. Immunohistochemistry showed that the expression of CD31, CD34, F8, s-100, desmin, SMA, and CD99 was negative, whereas the expression of β-catenin, BCL-2, SATB-2, and P16 was positive. CD68 and MDM-2 showed low expression, while 50% of the cells were positive for Ki-67 expression. No abnormal concentration of radioactivity was found on the bone scan with 99mTc-MDP after the operation, further ruling out the occurrence of other bone tumors. The patient was diagnosed with primary extraskeletal osteosarcoma. It is necessary for multidisciplinary teams to diagnose malignant extraskeletal osteosarcomas.

BackgroundThe analgesic effect produced by the intra-arterial injection of lidocaine in patients undergoing uterine artery embolization has been proven to be safe and effective. Nevertheless, a significant degree of pain is typically experienced after the operation, and pain management is crucial. Methylprednisolone, which provides an anti-inflammatory effect, is widely used in the treatment of several diseases. To date, methylprednisolone has not been used after uterine artery embolization.MethodsA total of 131 patients with uterine leiomyoma were retrospectively enrolled. Forty-five patients (control group) were treated with embolized microspheres for bilateral uterine artery embolization. Fifty (study group) and 36 (lidocaine group) patients were administered lidocaine mixed with embolized microspheres during embolization, and in addition, the study group was administered methylprednisolone. Completed pain scales at different time points during surgery were obtained from patients undergoing uterine artery embolization. Efficacy against pain was evaluated by comparing the pain score, inflammatory index, and use of sufentanil within 24 h followed by a Kruskal-Wallis Test and a least significant difference post-hoc analysis.ResultsThe postoperative pain scores at 1, 4, and 7 h after uterine artery embolization in the study group (3.08 ± 2.09, 2.46 ± 1.93, and 2.38 ± 1.85, respectively) were significantly lower than those in the control group (4.84 ± 2.36, 4.16 ± 1.87, and 3.56 ± 1.93, respectively) and the lidocaine group (3.50 ± 2.10, 3.30 ± 1.88, and 3.28 ± 1.89, respectively). At the first 24 h after embolization, the total usage of sufentanil in the study group (31.4 ± 4.16) was significantly lower than those in the control group (45.7 ± 6.51) and the lidocaine group (38.3 ± 6.25). At 1 and 4 h, the pain scores of the lidocaine group were significantly lower than those of the control group. In addition, at the first 24 h after embolization, the total usage of sufentanil in the lidocaine group was significantly lower than that in the control group.ConclusionLidocaine in combination with methylprednisolone can significantly alleviate pain and reduce the usage of sufentanil after bilateral uterine artery embolization. Thus, methylprednisolone is a recommended addition to the therapeutic regimen after embolization.

Sitosterolemia (OMIM ##210250), also known as phytosterolemia, is a rare autosomal recessive disorder caused by mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) or member 8 (ABCG8) genes. This leads to abnormal functions of the transporter sterolin-1 protein encoded by ABCG5 and sterolin-2 protein encoded by ABCG8, respectively, which can hinder the formation of stable ABCG5/G8 heterodimers, decreasing its ability to transport sterols. As a result, phytosterols in tissue or plasma are significantly increased, leading to early onset atherosclerosis-related diseases and xanthelasma of tendons and skin. In this study, whole exome sequencing was performed on a Chinese Han proband with sitosterolemia to capture the target gene and screen for suspected pathogenic mutations. Sanger sequencing of the family members was performed to verify the relationship between family genetics and phenotypes. The structural and functional changes in the transporter sterolin-1 protein after the responsible mutation were predicted using bioinformatics analysis. A novel compound heterozygous mutation in the ABCG5 gene (NM_022436) was identified in a proband with sitosterolemia, one of which was inherited from the father: c.296T >G (p.M99R), and one from the mother: c.−76 C >T. SIFT, Polyphen2, and Mutation Taster software predicted that p.M99R may be the responsible variant and a novel variant. RNAFold software predicts that c.−76 C >T may affect the transcriptional information or the binding of RNA binding proteins by regulating the structure of RNA, and ultimately affect gene transcription or RNA stability and translation. Swiss model software predicts that the amino acid sequence around p.M99R is highly conserved, and p.M99R leads to instability of the tertiary structure of the ABCG5/ABCG8 heterodimer. GPS 5.0 predicted that M99R affects the phosphorylation of nearby amino acid sequences, and DUET and VarSite software predicted that M99R affects the stability of sterolin-1 and cause disease. The p.M99R and c.−76 C >T mutations led to the formation of unstable heterodimers, which disturbed sterol absorption and excretion in vivo. The compound heterozygous variants c.296 T >G (p.m99r) and C.−76 C >T on exon 3 of ABCG5 in this family may be the molecular genetic basis of sitosterolemia.

BackgroundBronchial artery aneurysm (BAA) is a rare disease. Rupture of BAA can lead to life-threatening hemoptysis, and once diagnosed, treatment is needed regardless of symptoms. Transcatheter artery embolization is the first choice of treatment because it is minimally invasive and effective. This study aimed to retrospectively compare the embolization treatment of a case of true BAA and that of a pseudobranchial aneurysm and explore the choice of embolization method for BAA with short neck or no neck.Materials and MethodsEmbolization treatment and imaging characteristics of one case of true BAA and one case of pseudobronchial aneurysm admitted to our hospital were analyzed retrospectively. Embolization methods and therapeutic effects of two cases of BAAs were compared.ResultsCase 1 was that of an intact true BAA inside the mediastinum located at the opening of the bronchial artery. The distal end of the aneurysm was embolized, and tumor cavity was occluded. No recurrence of BAA was found after the operation. Case 2 was that of a ruptured and hemorrhagic pseudobronchial aneurysm of the mediastinum. Coil embolization combined with covered stent graft exclusion of the thoracic aorta were performed, and the left bronchial artery and BAA were almost occluded. Nine months postoperatively, the mediastinal hematoma was almost completely absorbed.ConclusionEndovascular embolization has become the most commonly used for the treatment of BAA. Different methods should be selected according to the location and nature of the aneurysm.

Abstract Background New therapeutic drugs are urgently needed against visceral leishmaniasis because current drugs, such as pentavalent antimonials and miltefosine, produce severe side effects and development of resistance. Whether cyclosporine A (CsA) and its derivatives can be used as therapeutic drugs for visceral leishmaniasis has been controversial for many years. Methods In this study, we evaluated the efficacy of CsA and its derivative, dihydrocyclosporin A (DHCsA-d), against promastigotes and intracellular amastigotes of Leishmania donovani. Sodium stibogluconate (SSG) was used as a positive control. Results Our results showed that DHCsA-d was able to inhibit the proliferation of L. donovani promastigotes (IC50: 21.24 μM and 12.14 μM at 24 h and 48 h, respectively) and intracellular amastigotes (IC50: 5.23 μM and 4.84 μM at 24 and 48 h, respectively) in vitro, but CsA treatment increased the number of amastigotes in host cells. Both DHCsA-d and CsA caused several alterations in the morphology and ultrastructure of L. donovani, especially in the mitochondria. However, DHCsA-d showed high cytotoxicity towards cells of the mouse macrophage cell line RAW264.7, with CC50 values of 7.98 μM (24 h) and 6.65 μM (48 h). Moreover, DHCsA-d could increase IL-12, TNF-α and IFN-γ production and decrease the levels of IL-10, IL-4, NO and H2O2 in infected macrophages. On the contrary, CsA decreased IL-12, TNF-α, and IFN-γ production and increased the levels of IL-10, IL-4, NO and H2O2 in infected macrophages. The expression of L. donovani cyclophilin A (LdCyPA) in promastigotes and intracellular amastigotes and the expression of cyclophilin A (CyPA) in RAW 264.7 cells were found to be significantly downregulated in the CsA-treated group compared to those in the untreated group. However, no significant changes in LdCyPA and CyPA levels were found after DHCsA-d or SSG treatment. Conclusions Our findings initially resolved the dispute regarding the efficacy of CsA and DHCsA-d for visceral leishmaniasis treatment. CsA showed no significant inhibitory effect on intracellular amastigotes. DHCsA-d significantly inhibited promastigotes and intracellular amastigotes, but it was highly cytotoxic. Therefore, CsA and DHCsA-d are not recommended as antileishmanial drugs.

Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013.

Background. Brugada syndrome is a hereditary cardiac disease associated with mutations in ion channel genes. The clinical features include ventricular fibrillation, syncope, and sudden cardiac death. A family with Brugada syndrome with sudden cardiac death was analyzed to locate the associated mutation in the SCN5A gene. Methods and Results. Three generations of a Han Chinese family with Brugada syndrome were recruited in the study; their clinical phenotype data were collected and DNA samples extracted from the peripheral blood. Next-generation sequencing was carried out in the proband, and candidate genes and mutations were screened using the full exon capture technique. The family members who participated in the survey were tested for possible mutations using Sanger sequencing. Six family members were diagnosed with Brugada syndrome, including four asymptomatic patients. A newly discovered heterozygous mutation in the proband was located in exon 25 of SCN5A (NM_000335.5) at c.4313dup(p.Trp1439ValfsTer32). Among the surviving family members, only those with a Brugada wave on their electrocardiogram carried the c.4313dup(p.Trp1439ValfsTer32) variant. Bioinformatics prediction revealed that the frameshift of the c.4313dup (p.Trp1439ValfsTer32) mutant led to a coding change of 32 amino acids, followed by a stop codon, resulting in a truncated protein product. Conclusion. The newly discovered mutation site c.4313dup(p.Trp1439ValfsTer32) in exon 25 of SCN5A may be the molecular genetic basis of the family with Brugada syndrome.

Piezoelectric atomization, which breaks liquid into tiny droplets, is widely used in aerospace, medicine, and health. Most research in piezoelectric atomizers has increased the atomization amount by improving mechanical structure and optimizing the vibration characteristics. However, as the core component of the atomizer is to realize atomization using the dynamic conical angle effect, the micro-tapered hole on the atomizing sheet has not been deeply studied. To eliminate the negative influence of the uneven burr caused by the hole machining process on the atomizing sheet, electrolytic polishing processing is proposed in this study to improve the quality of the micro-tapered holes. First, a theoretical model of the atomization amount and the conical angle is established. Second, the hole diameter and burr height are measured using a microscope, and the effectiveness of polishing on the burr removal of holes is verified. Lastly, the relationship between the conical angle and atomization amount is determined through an atomization amount experiment, which guides the revision of the theoretical model. The experimental results show that when the conical angle is 48,267° (the polishing time is 5 min), the atomization amount reaches a maximum of 5.202 mL/min, which is 3.93 times larger than that of the untreated one. This study demonstrates that polishing can effectively remove burr in the process of hole machining, which provides theoretical guidance for improving the quality of atomization sheets, and will further improve the atomization number of atomizers.

In applying large-momentum effective theory, renormalization of the Euclidean correlators in lattice regularization is a challenge due to linear divergences in the self-energy of Wilson lines. Based on lattice QCD matrix elements of the quasi-PDF operator at lattice spacing a=0.03fm ∼ 0.12fm with clover and overlap valence quarks on staggered and domain-wall sea, we design a strategy to disentangle the divergent renormalization factors from finite physics matrix elements, which can be matched to a continuum scheme at short distance such as dimensional regularization and minimal subtraction. Our results indicate that the renormalization factors are universal in the hadron state matrix elements. Moreover, the physical matrix elements appear independent of the valence fermion formulations. These conclusions remain valid even with HYP smearing which reduces the statistical errors albeit reducing control of the renormalization procedure. Moreover, we find a large non-perturbative effect in the popular RI/MOM and ratio renormalization scheme, suggesting favor of the hybrid renormalization procedure proposed recently.

We present the first lattice-QCD calculation of the kaon distribution amplitude using the large-momentum effective theory (LaMET) approach. The momentum-smearing technique has been implemented to improve signals at large meson momenta. We subtract the power divergence due to Wilson line to high precision using multiple lattice spacings. The kaon structure clearly shows an asymmetry of the distribution amplitude around x=1/2, a clear sign of its skewness. Our result also prefers a broader distribution than the asymptotic form. We also study the leading SU(3) flavor symmetry breaking relations for the pion, kaon and eta meson distribution amplitudes, and the results are consistent with the prediction from chiral perturbation theory.

At present, the micropumps are usually adopted in microelectromechanical systems (MEMS) process, which is characterized by high technical complexity and expense, to obtain micro-scale internal channels. Moreover, the MEMS process is more suitable for the 2.5-dimensional channels. This paper presents a 3-dimensional vortex tube-based valveless piezoelectric micropump with low cost and high accuracy, and the projection micro litho stereo exposure (PμLSE) technology is applied to manufacture the prototype of the micropump. The working principle of the piezoelectric micropump is analyzed, and the flow resistance of the vortex diode is calculated numerically. Then, the performance and 3D morphology measurement of the micropump are conducted. The results demonstrate that the inner surface of the channel is uniform and the surface roughness is small. By comparing and analyzing the output performances between two prototypes manufactured by the PμLSE technology, the stability of the PμLSE technology is confirmed. This paper provides a fast and cheap method for manufacturing a 3D micropump, and the proposed approach can also be further adopted in fabricating such micro-stereoscopic structure devices.

In large-momentum effective theory (LaMET), calculating parton physics starts from calculating coordinate-space-z correlation functions h˜(z,a,Pz) in a hadron of momentum Pz in lattice QCD. Such correlation functions involve both linear and logarithmic divergences in lattice spacing a, and thus need to be properly renormalized. We introduce a hybrid renormalization procedure to match these lattice correlations to those in the continuum MS‾ scheme, without introducing extra non-perturbative effects at large z. We analyze the effect of O(ΛQCD) ambiguity in the Wilson line self-energy subtraction involved in this hybrid scheme. To obtain the momentum-space distributions, we recommend to extrapolate the lattice data to the asymptotic z-region using the generic properties of the coordinate space correlations at moderate and large Pz, respectively.

A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Different mutation sites in APC are associated with the severity of FAP, risks of carcinogenesis, and extraintestinal manifestations. We used next-generation sequencing (NGS) and capture techniques to screen suspected mutation points in the proband in this pedigree. Using modified Sanger sequencing, we identified members of the family who were carriers of this variant and whether this segregated well with disease occurrence. FAP family members had multiple adenomatous polyps in their gastrointestinal tracts, some of which developed into cancer with age. Two subjects presented a rare common bile duct polyp phenotype. No extraintestinal manifestations were observed. A heterozygous frameshift mutation in APC exon 16 (NM_000038.6) was observed in the proband and in other patients: c.3260_3261del (p.Leu1087GlnQfs∗31) (rs587782305); the variant call format was CCT/C. Due to the deletion of two bases, a stop codon appeared after 31 amino acids, and the protein was truncated prematurely, which affected the conformation of the protein. Pedigree genetic linkage analysis showed that the clinical phenotype cosegregated with the APC mutation p.L1087fs. This mutation may be the pathogenic in this FAP family and responsible for this rare common bile duct polyp.

We present the first lattice calculation of the valence-quark generalized parton distribution (GPD) of the pion using the large-momentum effective theory (LaMET) approach. We focus on the zero-skewness limit, where the GPD has a probability-density interpretation in the longitudinal Bjorken x and the transverse impact-parameter distributions. Our calculation is done using clover valence fermions on an ensemble of gauge configurations with 2+1+1 flavors (degenerate up/down, strange and charm) of highly improved staggered quarks (HISQ) with lattice spacing a≈0.12 fm, box size L≈3 fm and pion mass mπ≈310 MeV. The parton distribution function and the form factor are reproduced as special limits of the GPD as expected. Due to the large errors, this exploratory study does not show a clear preference among different model assumptions about the kinematic dependence of the GPD. To discriminate between these assumptions, future studies using higher-statistics data will be crucial.

Abstract Following the proposal in (Braun and Müller. Eur Phys J C55:349, 2008), we study the feasibility to calculate the pion distribution amplitude (DA) from suitably chosen Euclidean correlation functions at large momentum. In our lattice study we employ the novel momentum smearing technique (Bali et al. Phys Rev D93:094515, 2016; Bali et al. Phys Lett B774:91, 2017). This approach is complementary to the calculations of the lowest moments of the DA using the Wilson operator product expansion and avoids mixing with lower dimensional local operators on the lattice. The theoretical status of this method is similar to that of quasi-distributions (Ji. Phys Rev Lett 110:262002, 2013) that have recently been used in (Zhang et al. Phys Rev D95:094514, 2017) to estimate the twist two pion DA. The similarities and differences between these two techniques are highlighted.

The control plane has low reliability and controller loads were unbalanced in distributed software defined networks,and a multi-controller balancing deployment strategy based on reliability evaluation was proposed.Firstly,node reliability was evaluated by weighting node efficiency and path quality,optimizing the controller location with balancing factor.Then based on improved k-center clustering,the redundant functions was introduced and the switch allocation was completed according to node attractiveness degree and controller load balancing rate,achieving a reasonable SDN sub-domain planning.The simulations show that compared with the existing strategy the number of required controllers is reduced by an average of 22.1%.The control plane elasticity is enhanced,and the controller load balancing performance has been improved significantly.

Large-Momentum Effective Theory (or LaMET) advocated by the present authors provides a direct approach to simulate parton physics in Euclidean lattice QCD theory. Recently, there has been much interest in this theory in the literature, with some questioning its validity and effectiveness. Here we provide some discussions aiming at a further exposition of this approach. In particular, we explain why it does not have the usual power divergence problem in lattice QCD calculations for the moments of parton distributions. The only power divergence in the LaMET approach comes from the self-energy of the Wilson lines which can be properly factorized. We show that although the Ioffe-time distribution provides an alternative way to extract the parton distribution from the same lattice observables, it also requires the same large momentum (or short distance) limit as in LaMET to obtain a precision calculation. With a proper quantification of errors, both extraction methods shall be compared with the same lattice data.

In the distributed software defined network，switch se1ects rigid migration object and has coordinating migration prob1ems.The prime switch migration scheme into two processes inc1uded se1ecting migration object and dep1oying switches dynamica11y was optimized，a switch competing migration a1gorithm was proposed based on process optimization.First1y，it synthesized de1ay，traffic and fai1ure cost，and se1ected migration object.Then，according to surviva1 time，migration time and dynamic 1oad thresho1d of contro11er，switches were migrated into object contro11er through iterative competition.Resu1ts show that compared with the existed migration a1gorithms the proposed a1gorithm se1ects more reasonab1e migration objects，avoiding migration conf1ict between switches，and contro11er 1oad ba1ancing rate has been promoted to 25.6% average1y.

Recent developments showed that hadron light-cone parton distributions could be directly extracted from spacelike correlators, known as quasi parton distributions, in the large hadron momentum limit. Unlike the normal light-cone parton distribution, a quasi parton distribution contains ultraviolet (UV) power divergence associated with the Wilson line self energy. We show that to all orders in the coupling expansion, the power divergence can be removed by a “mass” counterterm in the auxiliary z-field formalism, in the same way as the renormalization of power divergence for an open Wilson line. After adding this counterterm, the quasi quark distribution is improved such that it contains at most logarithmic divergences. Based on a simple version of discretized gauge action, we present the one-loop matching kernel between the improved non-singlet quasi quark distribution with a lattice regulator and the corresponding quark distribution in dimensional regularization.

A broadband visible light-absorbing [70]fullerene-BODIPY-triphenylamine triad (C70-B-T) has been synthesized and applied as a heavy atom-free organic triplet photosensitizer for photooxidation. By attaching two triphenylmethyl amine units (TPAs) to the π-core of BODIPY via ethynyl linkers, the absorption range of the antenna is extended to 700 nm with a peak at 600 nm. Thus, the absorption spectrum of C70-B-T almost covers the entire UV–visible region (270–700 nm). The photophysical processes are investigated by means of steady-state and transient spectroscopies. Upon photoexcitation at 339 nm, an efficient energy transfer (ET) from TPA to BODIPY occurs both in C70-B-T and B-T, resulting in the appearance of the BODIPY emission at 664 nm. Direct or indirect (via ET) excitation of the BODIPY-part of C70-B-T is followed by photoinduced ET from the antenna to C70, thus the singlet excited state of C70 (1C70*) is populated. Subsequently, the triplet excited state of C70 (3C70*) is produced via the intrinsic intersystem crossing of C70. The photooxidation ability of C70-B-T was studied using 1,5-dihydroxy naphthalene (DHN) as a chemical sensor. The photooxidation efficiency of C70-B-T is higher than that of the individual components of C70-1 and B-T, and even higher than that of methylene blue (MB). The photooxidation rate constant of C70-B-T is 1.47 and 1.51 times as that of C70-1 and MB, respectively. The results indicate that the C70-antenna systems can be used as another structure motif for a heavy atom-free organic triplet photosensitizer.

We present the first lattice-QCD calculation of the isovector polarized parton distribution functions (both helicity and transversity) using the large-momentum effective field theory (LaMET) approach for direct Bjorken-x dependence. We first review the detailed steps of the procedure in the unpolarized case, then generalize to the helicity and transversity cases. We also derive a new mass-correction formulation for all three cases. We then compare the effects of each finite-momentum correction using lattice data calculated at Mπ≈310 MeV. Finally, we discuss the implications of these results for the poorly known antiquark structure and predict the sea-flavor asymmetry in the transversely polarized nucleon.

The reported effects of the glutathione S-transferase (GSTs) genes (GSTM1, GSTT1, and GSTP1) on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype (Ile/Val + Val/Val) with idiopathic infertility risk (odds ratio [OR]: 1.53; 95% confidence interval [CI]: 1.11-2.11; P = 0.009). Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTT1-null and GSTP1 (Ile/Val + Val/Val) (OR: 2.17; 95% CI: 1.43-3.31; P = 0.0002). These results suggest an increased risk of the GSTP1 variant genotype (Ile/Val + Val/Val) for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 (especially the former) in modulating the risk of male infertility in males from Sichuan, southwest China.

We provide a theoretical basis for understanding the spin structure of the proton in terms of the spin and orbital angular momenta of free quarks and gluons in Feynman's parton picture. We show that each term in the Jaffe–Manohar spin sum rule can be related to the matrix element of a gauge-invariant, but frame-dependent operator through a matching formula in large-momentum effective field theory. We present all the matching conditions for the spin content at one-loop order in perturbation theory, which provide a basis to calculate parton orbital angular momentum in lattice QCD at leading logarithmic accuracy. Keywords: Proton spin sum rule, Lattice QCD

From the microscopic and quantitative viewpoints,the connotation of the structural flexibility of reconfigurable networks was explored.More accurately,a key feature,i.e.,the dynamic data channel varying with service demands,of reconfigurable networks was first exhibited and explained.Four dominant implications of the flexibility were then revealed as gradually mapping to demands,keeping global performance good,implicit isolation,and self-driven control.Finally,related quantitative models and methods for both determining the stable deviation of outcomes from demands and computing the volume of resource dynamically reconfigured were investigated by using the exponentially moving average,the n:m voting scheme,Markov decision processes (MDP) and reinforcement learning,respectively.

As the long wavelength limit of the AdS/CFT correspondence, the gravity/fluid correspondence has been shown to be a useful tool for extracting properties of the fluid on the boundary dual to the gravity in the bulk. In this paper, after briefly reviewing the algorithm of gravity/fluid correspondence, we discuss the results of its application on bulk gravity with a U(1) gauge field. In the presence of a U(1) gauge field, the dual fluid possesses more interesting properties such as its charge current. Furthermore, an external field Aμext could affect the charge current, and the U(1) Chern-Simons term also induces extra structures to the dual current giving anomalous transport coefficients.

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models. Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+- K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's diseaseassociated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish. Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+- ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio. Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish. [ABSTRACT FROM AUTHOR]

Proofreading (editing) of mischarged tRNAs by cytoplasmic aminoacyl-tRNA synthetases (aaRSs), whose impairment causes neurodegeneration and cardiac diseases, is of high significance for protein homeostasis. However, whether mitochondrial translation needs fidelity and the significance of editing by mitochondrial aaRSs have been unclear. Here, we show that mammalian cells critically depended on the editing of mitochondrial threonyl-tRNA synthetase (mtThrRS, encoded by Tars2), disruption of which accumulated Ser-tRNAThr and generated a large abundance of Thr-to-Ser misincorporated peptides in vivo. Such infidelity impaired mitochondrial translation and oxidative phosphorylation, causing oxidative stress and cell cycle arrest in the G0/G1 phase. Notably, reactive oxygen species (ROS) scavenging by N-acetylcysteine attenuated this abnormal cell proliferation. A mouse model of heart-specific defective mtThrRS editing was established. Increased ROS levels, blocked cardiomyocyte proliferation, contractile dysfunction, dilated cardiomyopathy, and cardiac fibrosis were observed. Our results elucidate that mitochondria critically require a high level of translational accuracy at Thr codons and highlight the cellular dysfunctions and imbalance in tissue homeostasis caused by mitochondrial mistranslation. [ABSTRACT FROM AUTHOR]