LINC01572 promotes the malignant progression of lung adenocarcinoma by modulating p53 mediated by miRNA-338-5p/TTK axis.

OBJECTIVES: Lung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored. METHODS: In this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis. KEY FINDINGS: The results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo. CONCLUSIONS: Our findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.

Biochemical and molecular analysis of pediatric patients with metachromatic leukodystrophy in South China: functional characterization of five novel ARSA variants.

Metachromatic leukodystrophy (MLD) is a rare hereditary neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). This study described the clinical and molecular characteristics of 24 Chinese children with MLD and investigated functional characterization of five novel ARSA variants. A retrospective analysis was performed in 24 patients diagnosed with MLD at Guangzhou Women and Children's Medical Center in South China. Five novel mutations were further characterized by transient expression studies. We recruited 17 late-infantile, 3 early-juvenile, 4 late-juvenile MLD patients. In late-infantile patients, motor developmental delay and gait disturbance were the most frequent symptoms at onset. In juvenile patients, cognitive regression and gait disturbance were the most frequent chief complaints. Overall, 25 different ARSA mutations were identified with 5 novel mutations.The most frequent alleles were p.W320* and p.G449Rfs. The mutation p.W320*, p.Q155=, p.P91L, p.G156D, p.H208Mfs*46 and p.G449Rfs may link to late-infantile type. The novel missense mutations were predicted damaging in silico. The bioinformatic structural analysis of the novel missense mutations showed that these amino acid replacements would cause severe impairment of protein structure and function. In vitro functional analysis of the six mutants, showing a low ARSA enzyme activity, clearly demonstrated their pathogenic nature. The mutation p.D413N linked to R alleles. In western blotting analysis of the ARSA protein, the examined mutations retained reduced amounts of ARSA protein compared to the wild type. This study expands the spectrum of genotype of MLD. It helps to the future studies of genotype-phenotype correlations to estimate prognosis and develop new therapeutic approach.

Atypical phenotypes and novel OCRL variations in southern Chinese patients with Lowe syndrome.

BACKGROUND: Lowe syndrome is characterized by the presence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study presents a case of an atypical phenotype, investigates the genetic characteristics of eight children diagnosed with Lowe syndrome in southern China, and performs functional analysis of the novel variants. METHODS: Whole-exome sequencing was conducted on eight individuals diagnosed with Lowe syndrome from three medical institutions in southern China. Retrospective collection and analysis of clinical and genetic data were performed, and functional analysis was conducted on the five novel variants. RESULTS: In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not present with congenital cataracts. Common features among all patients included cognitive impairment, short stature, and low molecular weight proteinuria. Eight variations in the OCRL gene were identified, encompassing three previously reported and five novel variations. Among the novel variations, three nonsense mutations were determined to be pathogenic, and two patients harboring novel missense variations of uncertain significance exhibited severe typical phenotypes. Furthermore, all novel variants were associated with altered protein expression levels and impacted primary cilia formation. CONCLUSION: This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and performs a functional analysis of novel variants in the OCRL gene, thereby expanding the understanding of the clinical manifestations and genetic diversity associated with Lowe syndrome.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

Clinical manifestations and genetic mutation analysis of patients with mucopolysaccharidosis type VII in China.

OBJECTIVE: This study aimed to explore the clinical and genetic features of Chinese patients with mucopolysaccharidosis type VII (MPS VII), thereby improving early detection, disease management, and patient outcomes. METHODS: A retrospective review of medical records for five patients presenting with coarse facial features, rib protrusion, chest deformities, and scoliosis was conducted. Exome sequencing was employed to identify causative genetic mutations. RESULTS: The study comprised five patients (four males, one female) with disease onset at six months of age (range: 0-1.5 years). Common symptoms included coarse facial features, skeletal abnormalities, delayed motor and language development, and intellectual disability. Approximately 80% of the patients exhibited multiple skeletal dysplasias, enlarged adenoids or tonsils, and snoring; 60% had hernias; 40% reported hearing loss and hepatosplenomegaly. Less frequent manifestations were short stature, valvular heart disease, non-immune hydrops fetalis, and corneal opacity. All patients demonstrated elevated urine glycosaminoglycans levels and absent ß-glucuronidase activity in leukocytes. Exome sequencing identified compound heterozygous mutations in the GUSB gene in all four tested patients, uncovering seven mutations in total, three of which were novel (c.189G > A, c.869C > T, and c.1745 T > C). Furthermore, prenatal diagnosis through chorionic villus sampling in subsequent pregnancies of one patient's mother revealed both fetuses had normal ß-glucuronidase activity and no disease-causing mutations in the GUSB gene. CONCLUSION: The study's patients all presented with classic symptoms of MPS VII due to ß-glucuronidase deficiency, with three new pathogenic mutations identified in the GUSB gene. Genetic counseling and prenatal testing were highlighted as crucial for disease prevention.

Two Chinese Patients of Auriculocondylar Syndrome 2: A Novel PLCB4 Splicing Variant and 5-Year Follow-up.

OBJECTIVE: Auriculocondylar syndrome (ARCND) is a set of rare craniofacial malformations characterized by variable micrognathia, ear malformations, and mandibular condyle hypoplasia, and other accompanying features with phenotypic complexity. ARCND2 caused by pathogenic variants in the PLCB4 gene is a very rare disease with less than 50 patients reported and only 36 different variants of the PLCB4 gene recorded in HGMD. This study aims to enrich the patient resources, clinical data and mutational spectrum of ARCND2. DESIGN: Case series study. SETTING: Guangzhou Women and Children's Medical Center and Guangdong Women and Children Hospital. PATIENTS: Two Chinese patients with ARCND2. MAIN OUTCOME MEASURES: Clinical, radiological and molecular findings. RESULTS: Both the two patients presented with craniofacial and ear malformations, and feeding difficulties. Whole exome sequencing identified two different variants of the PLCB4 gene in these two patients with a heterozygous allele and a de novo mode of inheritance respectively. Patient 1 carried a known pathogenic c.1861C > T(p.Arg621Cys) missense variant, whereas Patient 2 had a novel c.225 + 1G > A splicing variant. Sanger sequencing confirmed the presence of PLCB4 variants in the proband and absence in the unaffected parents. These two PLCB4 variants were suggested as disease-causing candidates for these two patients. During a 5-year follow-up, Patient 2 gradually manifested crowded teeth, underweight, motor delay and intellectual disability. CONCLUSIONS: In this study, we report two Chinese patients with ARCND2, describe their clinical and mutational features, and share a 5-year follow-up of one patient. Our study adds two additional patients to ARCND2, reveals a novel PLCB4 variant, and expands the phenotypic and genotypic spectrum.

Mechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model.

Dopa and tetrahydrobiopterin (BH4) supplementation are recommended therapies for the dopa-responsive dystonia caused by GTP cyclohydrolase 1 (GCH1, also known as GTPCH) deficits. However, the efficacy and mechanisms of these therapies have not been intensively studied yet. In this study, we tested the efficacy of dopa and BH4 therapies by using a novel GTPCH deficiency mouse model, Gch1KI/KI, which manifested infancy-onset motor deficits and growth retardation similar to the patients. First, dopa supplementation supported Gch1KI/KI mouse survival to adulthood, but residual motor deficits and dwarfism remained. Interestingly, RNAseq analysis indicated that while the genes participating in BH4 biosynthesis and regeneration were significantly increased in the liver, no significant changes were observed in the brain. Second, BH4 supplementation alone restored the growth of Gch1KI/KI pups only in early postnatal developmental stage. High doses of BH4 supplementation indeed restored the total brain BH4 levels, but brain dopamine deficiency remained. While total brain TH levels were relatively increased in the BH4 treated Gch1KI/KI mice, the TH in the striatum were still almost undetectable, suggesting differential BH4 requirements among brain regions. Last, the growth of Gch1KI/KI mice under combined therapy outperformed dopa or BH4 therapy alone. Notably, dopamine was abnormally high in more than half, but not all, of the treated Gch1KI/KI mice, suggesting the existence of variable synergetic effects of dopa and BH4 supplementation. Our results provide not only experimental evidence but also novel mechanistic insights into the efficacy and limitations of dopa and BH4 therapies for GTPCH deficiency.

Critical transition of thermal rectification on complex networks.

Thermal rectification is a mechanism that controls the direction of heat conduction, allowing it to flow freely in one direction and hindering it in the opposite direction. In this study, we propose a heat conduction model on a complex network where the node masses are non-uniformly distributed according to mi∼kiα. Our findings show that the existence of a critical point, α=1, determines the working mode of thermal rectification. For α>1, the working mode of thermal rectification is positive, whereas for α<1, the working mode is negative. Additionally, we discovered that this critical transition is a general phenomenon and does not vary with changes in network size, average degree, or degree distribution. By conducting theoretical analyses based on phonon spectra, we also identified the physical mechanism of the critical transition. These results provide a new approach to implement and enrich thermal diodes, opening up new possibilities for more efficient thermal management.

Semiconductivity induced by spin-orbit coupling in Pb9Cu(PO4)6O.

Recently, a possible room-temperature superconductor known as LK-99 (Pb10-xCux(PO4)6O (0.9 < x < 1.1)) has sparked a wave of research. However, many experimental works have proven that it is a semiconductor. At the same time, many theoretical works have reached the conclusion that it is a flat band metal. The inconsistency between theoretical and experimental works may be caused by neglecting the spin-orbit coupling effect in calculations. We performed calculations of electronic structure of Pb9Cu(PO4)6O with spin-orbit coupling, and the results show that it's indeed a semiconductor, not a metal. In the ferromagnetic state it is an indirect-bandgap semiconductor with a bandgap of 292 meV. While in the antiferromagnetic-A state, it is a direct-bandgap semiconductor with a bandgap of 300 meV. Our work provides a possible explanation for the contradictions of previous experiments and theories, and provides some theoretical basis for the potential application of Pb9Cu(PO4)6O as a semiconductor.

Prediction of 2D group-11 chalcogenides: insights into novel auxetic M2X (M = Cu, Ag, Au; X = S, Se, Te) monolayers.

Two-dimensional (2D) auxetic materials have recently attracted considerable research interest due to their excellent mechanical properties and diverse applications, surpassing those of three-dimensional (3D) materials. This study focuses on the theoretical prediction of mechanical properties and auxeticity in 2D M2X (M = Cu, Ag, Au; X = S, Se, Te) monolayers using first-principles calculations. Our results indicate that the dynamically stable monolayers include low-energy α-Cu2S, α-Cu2Se, α-Cu2Te, ß-Ag2S, ß-Ag2Se, α-Ag2Te, ß-Au2S, ß-Au2Se and α-Au2Te. These M2X monolayers possess positive Poisson's ratios (PR) ranging from 0.09 to 0.52, as well as Young's moduli ranging from 19.92 to 35.42 N m-1 in x and y directions. Specially, α-Cu2S exhibits the lowest negative PR in θ = 45° × n (n = 1, 2, 3, 4) directions. The Poisson's function (PF) can be adjusted by increasing tensile strains. The ß-phase monolayers exhibit positive PF with a linear change. Interestingly, the transition from positive to negative PF occurs in the α-Cu2S and α-Ag2Te monolayers at strains greater than +3% and +4%, respectively, while the α-Cu2Se, α-Cu2Te and α-Au2Te monolayers maintain positive PF within the range of 0% to +6% strains. Furthermore, taking α-Cu2S (α-Cu2Te) as an example, the mechanism underlying negative (positive) PF is demonstrated to involve increased (decreased) bond angles, decreased thickness, and weakened (enhanced) d(M)-p(X) orbital coupling. The findings of this study not only enrich the family of 2D group-11 chalcogenides but also provide insights into their mechanical properties, thereby expanding their potential applications in mechanics.

Roughness induced current reversal in fractional hydrodynamic memory.

The existence of a corrugated surface is of great importance and ubiquity in biological systems, exhibiting diverse dynamic behaviors. However, it has remained unclear whether such rough surface leads to the current reversal in fractional hydrodynamic memory. We investigate the transport of a particle within a rough potential under external forces in a subdiffusive media with fractional hydrodynamic memory. The results demonstrate that roughness induces current reversal and a transition from no transport to transport. These phenomena are analyzed through the subdiffusion, Peclet number, useful work, input power, and thermodynamic efficiency. The analysis reveals that transport results from energy conversion, wherein time-dependent periodic force is partially converted into mechanical energy to drive transport against load, and partially dissipated through environmental absorption. In addition, the findings indicate that the size and shape of ratchet tune the occurrence and disappearance of the current reversal, and control the number of times of the current reversal occurring. Furthermore, we find that temperature, friction, and load tune transport, resonant-like activity, and enhanced stability of the system, as evidenced by thermodynamic efficiency. These findings may have implications for understanding dynamics in biological systems and may be relevant for applications involving molecular devices for particle separation at the mesoscopic scale.

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family.

Rare genetic skeletal disorders (GSDs) remain the major problem in orthopedics and result in significant morbidity in patients, but the causes are highly diverse. Precise molecular diagnosis will benefit management and genetic counseling. This study aims to share the diagnostic experience on a three-generation Chinese family with co-occurrence of spondyloepiphyseal dysplasia (SED) and X-linked hypophosphatemia (XLH), and evaluate the therapeutic effects of two third-generation siblings. The proband, his younger brother, and mother presented with short stature, skeletal problems, and hypophosphatemia. His father, paternal grandfather, and aunt also manifested short stature and skeletal deformities. Whole exome sequencing (WES) of proband-brother-parents initially only found the proband and his younger brother had a pathogenic c.2833G > A(p.G945S) variant in the COL2A1 gene inherited from their father. Re-analysis of WES uncovered the proband and his younger brother also harbored a pathogenic ex.12 del variant in the PHEX gene transmitted from their mother. Sanger sequencing, agarose gel electrophoresis, and quantitative polymerase chain reaction proved these results. The proband and his younger brother were confirmed to have a paternally inherited SED and a maternally inherited XLH. During a 2.8-year follow-up, these two siblings remained short stature and hypophosphatemia, but their radiographic signs and serum bone alkaline phosphatase levels were improved with treatment of oral phosphate and calcitriol. Our study presents the first report of co-occurrence of SED and XLH, shows the possibility that two different rare GSDs co-exist in a single patient, and alerts clinicians and geneticists to be cautious about this condition. Our study also suggests that next-generation sequencing has limit in detecting exon-level large deletions.

'Candidatus Liberibacter asiaticus' secretory protein SDE3 inhibits host autophagy to promote Huanglongbing disease in citrus.

Antimicrobial acroautophagy/autophagy plays a vital role in degrading intracellular pathogens or microbial molecules in host-microbe interactions. However, microbes evolved various mechanisms to hijack or modulate autophagy to escape elimination. Vector-transmitted phloem-limited bacteria, Candidatus Liberibacter (Ca. Liberibacter) species, cause Huanglongbing (HLB), one of the most catastrophic citrus diseases worldwide, yet contributions of autophagy to HLB disease proliferation remain poorly defined. Here, we report the identification of a virulence effector in "Ca. Liberibacter asiaticus" (Las), SDE3, which is highly conserved among the "Ca. Liberibacter". SDE3 expression not only promotes the disease development of HLB and canker in sweet orange (Citrus sinensis) plants but also facilitates Phytophthora and viral infections in Arabidopsis, and Nicotiana benthamiana (N. benthamiana). SDE3 directly associates with citrus cytosolic glyceraldehyde-3-phosphate dehydrogenases (CsGAPCs), which negatively regulates plant immunity. Overexpression of CsGAPCs and SDE3 significantly inhibits autophagy in citrus, Arabidopsis, and N. benthamiana. Intriguingly, SDE3 undermines autophagy-mediated immunity by the specific degradation of CsATG8 family proteins in a CsGAPC1-dependent manner. CsATG8 degradation is largely rescued by treatment with an inhibitor of the late autophagic pathway, E64d. Furthermore, ectopic expression of CsATG8s enhances Phytophthora resistance. Collectively, these results suggest that SDE3-CsGAPC interactions modulate CsATG8-mediated autophagy to enhance Las progression in citrus.Abbreviations: ACP: asian citrus psyllid; ACD2: ACCELERATED CELL DEATH 2; ATG: autophagy related; Ca. Liberibacter: Candidatus Liberibacter; CaMV: cauliflower mosaic virus; CMV: cucumber mosaic virus; Cs: Citrus sinensis; EV: empty vector; GAPC: cytosolic glyceraldehyde-3-phosphate dehydrogenase; HLB: huanglongbing; H2O2: hydrogen peroxide; Las: liberibacter asiaticus; Laf: liberibacter africanus; Lam: liberibacter americanus; Pst: Pseudomonas syringae pv. tomato; PVX: potato virus X; ROS: reactive oxygen species; SDE3: sec-delivered effector 3; TEM: transmission electron microscopy; VIVE : virus-induced virulence effector; WT: wild-type; Xcc: Xanthomonas citri subsp. citri.

Tunable Schottky contacts in graphene/XAu4Y (X, Y = Se, Te) heterostructures.

Graphene-based (G-based) heterostructures have recently attracted considerable research interest in the field of two-dimensional nanodevices owing to their superior properties compared with those of separate monolayers. In this study, the electronic properties and Schottky barrier heights (SBHs) of G/XAu4Y (X, Y = Se, Te) heterostructures were systematically analyzed through first-principles calculations. G/SeAu4Se, G/SeAu4Te, and G/TeAu4Se are n-type Schottky contacts with Φn = 0.40, 0.38, and 0.55 eV respectively, whereas G/TeAu4Te is a p-type Schottky contact with Φp = 0.39 eV. In G-based heterostructures consisting of SeAu4Te that has a 0.22-Debye intrinsic dipole moment, the intrinsic dipole moments in different directions enhance or weaken the interfacial dipole moments corresponding to the charge transfer at the interface, resulting in different Φn values of G/SeAu4Te and G/TeAu4Se. Furthermore, vertical strain and external electric field, which influence charge transfer, are applied to G/XAu4Y heterostructures to modulate their SBHs. Taking G/TeAu4Te as an example, the p-type contact transforms into an almost ohmic contact with decreasing vertical strain or positive external electric field. The findings of this study can provide insights into the fundamental properties of G/XAu4Y for further research.

Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome.

Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH). Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis. Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age. Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.

Diagnosis of an intermediate case of maple syrup urine disease: A case report.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids (BCAAs). However, the clinical and metabolic screening is limited in identifying all MSUD patients, especially those patients with mild phenotypes or are asymptomatic. This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis. CASE SUMMARY: This study reports the diagnostic process of a boy with intermediate MSUD. The proband presented with psychomotor retardation and cerebral lesions on magnetic resonance imaging scans at 8 mo of age. Preliminary clinical and metabolic profiling did not support a specific disease. However, whole exome sequencing and subsequent Sanger sequencing at 1 year and 7 mo of age identified bi-allelic pathogenic variants of the BCKDHB gene, confirming the proband as having MSUD with non-classic mild phenotypes. His clinical and laboratory data were retrospectively analyzed. According to his disease course, he was classified into an intermediate form of MSUD. His management was then changed to BCAAs restriction and metabolic monitoring conforming to MSUD. In addition, genetic counseling and prenatal diagnosis were provided to his parents. CONCLUSION: Our work provides diagnostic experience of an intermediate MSUD case, suggesting that a genetic analysis is important for ambiguous cases, and alerts clinicians to avoid missing patients with non-classic mild phenotypes of MSUD.

Preparation of Heavily Doped P-Type PbSe with High Thermoelectric Performance by the NaCl Salt-Assisted Approach.

Thermoelectric (TE) technology, which can convert scrap heat into electricity, has attracted considerable attention. However, broader applications of TE are hindered by lacking high-performance thermoelectric materials, which can be effectively progressed by regulating the carrier concentration. In this work, a series of PbSe(NaCl)x (x = 3, 3.5, 4, 4.5) samples were synthesized through the NaCl salt-assisted approach with Na+ and Cl- doped into their lattice. Both theoretical and experimental results demonstrate that manipulating the carrier concentration by adjusting the content of NaCl is conducive to upgrading the electrical transport properties of the materials. The carrier concentration elevated from 2.71 × 1019 cm-3 to 4.16 × 1019 cm-3, and the materials demonstrated a maximum power factor of 2.9 × 10-3 W m-1 K-2. Combined with an ultralow lattice thermal conductivity of 0.7 W m-1 K-1, a high thermoelectric figure of merit (ZT) with 1.26 at 690 K was attained in PbSe(NaCl)4.5. This study provides a guideline for chemical doping to improve the thermoelectric properties of PbSe further and promote its applications.

Emergence of macroscopic directional motion of deformable active cells in confined structures.

There is now growing evidence of collective turbulentlike motion of cells in dense tissues. However, how to control and harness this collective motion is an open question. We investigate the transport of deformable active cells in a periodically asymmetric channel by using a phase-field model. We demonstrate that collective turbulent-like motion of cells can power and steer the macroscopic directional motion through the ratchet channel. The active intercellular forces proportional to the deformation of cells can break thermodynamical equilibrium and induce the directional motion. This directional motion is caused by the ratchet effect rather than the spontaneous symmetry breaking. The motion direction is determined by the asymmetry of the channel. Remarkably, there exits an optimal nonequilibrium driving (depending on the active strength, the elasticity, and the packing fraction) at which the average velocity reaches the maximum. In addition, the optimized packing fraction and the optimized minimum width of the channel can facilitate the directional motion of cells. Our findings are relevant to understanding how macroscopic directional motion relates to the local force transmission mediated by cell-cell contacts in cellular monolayers.

Features of BSCL2 related congenital generalized lipodystrophy in China: long-term follow-up of three patients and literature review.

OBJECTIVES: Congenital generalized lipodystrophy (CGL) is a group of rare autosomal inherited diseases characterized by a widespread loss of adipose tissue. The main purpose of this study was to evaluate the features of Chinese patients with CGL2. METHODS: Three patients diagnosed with CGL2 from our center were reviewed. Data on clinical features, results of laboratory analyses, and previous treatments were retrospectively collected. This study also reviewed studies that reported patients diagnosed with CGL2 in the last 30 years. RESULTS: All patients presented a lack of subcutaneous fat, hypertriglyceridemia, reversed triangular faces, acanthosis nigricans, and hepatomegaly within the first six months of life. All three patients developed splenomegaly, and mental retardation in later life. Dietary control dramatically lowered triglyceride levels in all patients. One patient presented with diabetes mellitus at 1 year-old. Although combined therapy with low fat diet and metformin maintained normal levels of blood lipid and glucose, this patient developed hypertrophic cardiomyopathy at the age of three. By a literature review on all Chinese cases with CGL2, it is known that classic manifestations such as hypertriglyceridemia, hepatomegaly and diabetes mellitus can occur shortly after birth, and early diagnosis and treatment can improve quality of life. In this cohort, the most frequent variations are c.782dupG and c.974dup in the BSCL2 gene. However, the same genotype may have different clinical phenotypes in patients with CGL2. CONCLUSIONS: This study not only described the clinical and genetic features of three patients with CGL2 in China, but also reviewed literature about CGL2 around the world.

Clinical characteristics and long-term outcomes of 12 children with vitamin D-dependent rickets type 1A: A retrospective study.

Purpose: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by deficiency of the CYP27B1 gene. This study aims to investigate the phenotypic and genotypic features of VDDR1A children in southern China and evaluate the long-term therapeutic effects. Methods: Twelve children from southern China with VDDR1A were enrolled in this study. Their clinical, radiological, biochemical, and molecular findings were analyzed retrospectively. The rickets severity score (RSS), biochemical parameters, and height standard deviation score (HtSDS) were used to evaluate clinical outcomes. Results: Six males and six females were included in this VDDR1A cohort. The age of onset was from 6 months to 1.8 years, and the age at diagnosis was 2.1 ± 0.8 years. The most common clinical symptoms at diagnosis were delayed walking (10/12) and severe growth retardation (9/12). HtSDS at diagnosis was negatively associated with age (p < 0.05). All patients presented with hypocalcemia, hypophosphatemia, increased serum alkaline phosphatase and parathyroid hormone, and high RSS at diagnosis. Two allelic variants of the CYP27B1 gene were identified in all patients, including nine different variants, four known and five novel, with c.1319_1325dupCCCACCC(p.Phe443Profs*24) being the most frequent. All patients were treated with calcitriol and calcium after diagnosis, and all patients but one were followed-up from 6 months to 15.6 years. HtSDS, RSS, and biochemical parameters were found to be improved during the first few years of the treatment. However, only five patients had good compliance. Although RSS and biochemical parameters were significantly improved, the HtSDS change was not significant from the time of diagnosis to the last visit, and seven patients remained of a short stature (HtSDS < -2). Conclusion: Our study extends the mutational spectrum of VDDR1A and finds a hotspot variant of the CYP27B1 gene in southern China. The results reconfirm the importance of early diagnosis and treatment compliance and reveal the challenge of height improvement in VDDR1A patients.