Observation of Odd-Parity Superconductivity with the Geshkenbein-Larkin-Barone Composite Rings.

Phase-sensitive measurements on a composite ring made of a superconductor of interest connected by a known singlet s-wave superconductor can unambiguously determine its pairing symmetry. In composite rings with epitaxial ß-Bi_{2}Pd and s-wave Nb, we have observed half-integer-quantum flux when Nb is connected to the opposite crystalline ends of ß-Bi_{2}Pd and integer-quantum flux when Nb is connected to the same crystalline ends of ß-Bi_{2}Pd. With ascending temperature, the half-integer-flux quantization transits to integer-flux quantization, before the eventual loss of phase coherence. These findings point to odd-parity pairing symmetry in superconducting ß-Bi_{2}Pd.

Prenatal diagnosis of Noonan syndrome in a set of monozygotic twins- a case report.

BACKGROUND: We report a pair of dichorionic diamniotic (DCDA) twin pregnancy affected by Noonan syndrome (NS) with a novel mutation of LZTR1 determined by genetic analysis. CASE PRESENTATION: A pregnant woman with monozygotic twins (DCDA) at 12 + 2 weeks gestation was referred to our center. This was her second pregnancy following a previous delivery of a healthy infant. Nuchal translucency of two fetuses was 11.2 mm (CRL 62.0 mm) and 6.9 mm (CRL 62.1 mm) respectively. Ultrasound examination indicated cystic hygroma and hypoplastic ear. The couple was not consanguineous, and both had normal phenotype. Familial hereditary disease was also excluded. Under ultrasound guidance, 30 mg of chorionic villi was obtained for karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), chromosomal microarray analysis(CMA), and Trio-whole-exome sequencing(WES) examination. We used the "target region capture and sequencing" for WES, and the BWA (Burrows Wheeler Aligner) Multi-Vision software package for the data analysis. The results of all these tests were normal except WES detected a c.427 A > G mutation in the exonic region of the LZTR1 gene and a p. Asn143Asp novel heterozygous mutation associated with NS in this pair of twins. In addition, WES suggested that the mutation in the twin fetuses originated from the mother. When the mother got the genetic test report, she came to our fetal medicine department for genetic counseling and she declined the appointment with a clinical geneticist. The couple opted to terminate the pregnancy. Because the patient did not choose to terminate the pregnancy at our hospital, we were unable to take further examination. With the help of colleagues in another hospital, photos of the fetuses were taken. Compared with the prenatal ultrasound results, the appearance of the "cystic hygroma" and "hypoplastic ear" was consistent with the ultrasound. The couple were depressed after knowing this pathogenic result and although we advised the mother to take further investigation, they refused. CONCLUSION: The mutant locus might be incompletely dominant, which led to an abnormal fetal phenotype such as cystic hygroma and hypoplastic ear.

Study on the controlled release and synergistic anti-oxidant activity in vitro and ex vivo of ligustrazine hydrochloride encapsulated into liposomes.

Ligustrazine with good antioxidant activity is one of the main active components of chuanxiong. We designed ligustrazine hydrochloride-loaded liposomes (LTH-L) by the thin film dispersion method. The particle size and zeta potential of liposomes was 118±10.61nm and -39.3±3.7mV, entrapment efficiency (EE%) was 75.05±10.67%. In vitro permeation across the dialysis membrane, the release rate (R%) of ligustrazine hydrochloride (LTH) and LTH-L were reached 80% and 60%. Ex Vivo transdermal behavior experiment showed the R% of LTH and LTH-L were between 30%-40%, the R% of LTH-L was slightly lower, because liposomes played the role on the sustained and controlled release of LTH. In addition, LTH, LTH-L and BL reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH) solution for two hours, the scavenge rates (SR%) were 55.06±2.73%, 11.3±0.03% and 37.25±1.12% respectively (P<0.001) and the SR% of LTH, LTH-L and BL reacted with H2O2 were 4.13±0.02%, 0.52±0.01% and 75.15±6.10%. The inhibit rate (IR%) of LTH, LTH-L and BL on malondialdehyde (MDA) in liver homogenate were 35.44±1.79%, 1.22±0.01% and 17.92±0.29% (P<0.001), the IR% were 30.82±0.93%, 1.7±0.01% and 25.19±0.60% (P<0.001) in anti-low density lipoprotein (LDL) oxidation experiments, perhaps LTH prepared into LTH-L can play a better antioxidant role.

Selective termination of the fetus in multiple pregnancies using ultrasound-guided radiofrequency ablation.

BACKGROUND: To evaluate the perinatal outcomes in women with selective termination using ultrasound-guided radiofrequency ablation (RFA). METHODS: Complicated monochorionic (MC) twin pregnancies and multiple pregnancies with an indication for selective termination by ultrasound-guided coagulation of the umbilical cord with RFA under local anesthesia between July 2013 and Jan 2020 were reviewed. We analyzed the indications, gestational age at the time of the procedure, cycles of RFA, duration of the procedure, and perinatal outcome. RESULTS: Three hundred and thirteen patients were treated during this period. Seven of whom were lost of follow-up. The remaining 306 cases, including 266 pairs of monochorionic diamniotic (MCDA) twins (86.93%), two pairs of monoamniotic twins (0.65%), 30 dichorionic triamniotic (DCTA) triplets (1%), and three monochorionic triamniotic (MCTA) triplets (0.98%), were analyzed. Indications included twin-to-twin transfusion syndrome (TTTS) (n = 91), selective fetal growth restriction (sFGR) (n = 83), severe discordant structural malformation (n = 78), multifetal pregnancy reduction (MFPR) (n = 78), twin reverse arterial perfusion sequence (TRAPS) (n = 19), and twin anemia-polycythemia sequence (TAPS) (n = 3). Upon comparison of RFA performed before and after 20 weeks, the co-twin loss rate (20.9% vs. 21.5%), the incidence of preterm premature rupture of membranes (PPROM) within 24 h (1.5% vs. 1.2%), and the median gestational age at delivery [35.93 (28-38) weeks vs. 36 (28.54-38.14) weeks] were similar (p > 0.05). CONCLUSIONS: RFA is a reasonable option when indicated in multiple pregnancies and complicated monochorionic pregnancies. In our experience, the overall survival rate was 78.76% with RFA in selective feticide, and early treatment increases the likelihood of survival for the remaining fetus because the fetal loss rate is similar before and after 20 weeks.

The application of late amniocentesis: a retrospective study in a tertiary fetal medicine center in China.

BACKGROUND: To assess the indications and complications of late amniocentesis and the advanced genetic test results in a tertiary university fetal medical medicine unit. METHODS: In this retrospective study, women that underwent amniocentesis at 24+ 0 to 39+ 4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy and compared with those who underwent the traditional amniocentesis at 16+ 0 to 23+ 6 weeks (control group). Information was retrieved from patient medical records, checked by research staff, and analyzed. RESULTS: Of the 1287 women (1321 fetuses) included in the late amniocentesis group, late detected sonographic abnormalities (85.5%) were the most common indication. The overall incidence of preterm birth and intrauterine demise after amniocentesis were 2.5 and 1.3%, respectively. Sixty-nine fetuses with aneuploidy (5.3%) and seventy-two fetuses with pathogenic copy number variations (5.5%) were identified by chromosomal microarray analysis. The maximal diagnostic yield (70%) was in the subgroup of fetuses with the abnormal diagnostic test results, followed by abnormal NIPT results (35.7%) and multiple abnormalities (23.8%). And 35.4% of the pregnancies were finally terminated. CONCLUSIONS: Due to the high detection rates of advanced genetic technologies and the safety of the invasive procedure (3.9% vs 4.0%), it is reasonable to recommend late amniocentesis as an effective and reliable method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Comprehensive genetic counseling is necessary.

Cryptochrome 2 from Lilium × formolongi Regulates Photoperiodic Flowering in Transgenic Arabidopsis thaliana.

The photoperiodic flowering pathway is essential for plant reproduction. As blue and ultraviolet-A light receptors, cryptochromes play an important role in the photoperiodic regulation of flowering. Lilium × formolongi is an important cut flower that flowers within a year after seed propagation. Floral induction is highly sensitive to photoperiod. In this study, we isolated the CRYPTOCHROME2 gene (LfCRY2) from L. × formolongi. The predicted LfCRY2 protein was highly homologous to other CRY2 proteins. The transcription of LfCRY2 was induced by blue light. LfCRY2 exhibits its highest diurnal expression during the floral induction stage under both long-day and short-day photoperiods. Overexpression of LfCRY2 in Arabidopsis thaliana promoted flowering under long days but not short days, and inhibited hypocotyl elongation under blue light. Furthermore, LfCRY2 was located in the nucleus and could interact with L. × formolongi CONSTANS-like 9 (LfCOL9) and A. thaliana CRY-interacting basic-helix-loop-helix 1 (AtCIB1) in both yeast and onion cells, which supports the hypothesis that LfCRY2 hastens the floral transition via the CIB1-CO pathway in a manner similar to AtCRY2. These results provide evidence that LfCRY2 plays a vital role in promoting flowering under long days in L. × formolongi.

Spin-Triplet Pairing State Evidenced by Half-Quantum Flux in a Noncentrosymmetric Superconductor.

A prime category of superconducting materials in which to look for spin-triplet pairing and topological superconductivity are superconductors without inversion symmetry. It is predicted that the broken parity symmetry gives rise to an admixture of spin-triplet and spin-singlet pairing states. However, experimental confirmation of pairing mixing in any material remains elusive. In this work, we perform a phase-sensitive experiment to examine the pairing state of noncentrosymmetric superconductor α-BiPd. The Little-Parks effect observed in mesoscopic polycrystalline α-BiPd rings reveals the presence of half-integer magnetic flux quantization, which provides a decisive evidence for the spin-triplet pairing state. We find both half-quantum fluxes and integer-quantum fluxes of different proportions, consistent with the scenario of an admixture of singlet-triplet pairing.

Polariton Electric-Field Sensor.

We experimentally demonstrate a dipolar polariton based electric-field sensor. We tune and optimize the sensitivity of the sensor by varying the dipole moment of polaritons. We show polariton interactions play an important role in determining the conditions for optimal electric-field sensing, and achieve a sensitivity of 0.12 V m^{-1} Hz^{-0.5}. Finally, we apply the sensor to illustrate that excitation of polaritons modifies the electric field in a spatial region much larger than the optical excitation spot.

Noninvasive prenatal diagnosis for Duchenne muscular dystrophy based on the direct haplotype phasing.

OBJECTIVE: We aimed to investigate the validity of noninvasive prenatal diagnosis (NIPD) based on direct haplotype phasing without the proband or other family members and its feasibility for clinical application in the case of Duchenne muscular dystrophy (DMD). METHODS: Thirteen singleton-pregnancy families affected by DMD were recruited. The pathogenic variants in the pregnant females have been identified by multiplex ligation-dependent probe amplification (MLPA). We resolved maternal haplotypes for each family by performing targeted linked-read sequencing of their high molecular weight DNA, respectively. Then, we integrated the maternal haplotypes and the targeted sequencing results of maternal plasma DNA to infer the fetal haplotype and the DMD gene variant status. The fetal genotypes were further validated by using chorionic villus sampling. RESULTS: The method of directly resolving maternal haplotype through targeted linked-read sequencing was smoothly performed in 12 participated families, but one failed (F11). The predicted variant status of 12 fetuses was correct, which had been confirmed by invasive prenatal diagnosis. CONCLUSION: Direct haplotyping of NIPD based on linked-read sequencing for DMD is accurate.

Acetaldehyde dehydrogenase 2 deficiency exacerbates cardiac fibrosis by promoting mobilization and homing of bone marrow fibroblast progenitor cells.

Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to investigate the effect of ALDH2 deficiency on cardiac fibrosis in transverse aortic constriction (TAC) induced pressure overload model in mice. Echocardiography and histological analysis revealed cardiac dysfunction and enhanced cardiac fibrosis in TAC-operated animals; ALDH2 deficiency further aggravated these changes. ALDH2 chimeric mice were generated by bone marrow (BM) transplantation of WT mice into the lethally irradiated ALDH2KO mice. The proportion of circulating fibroblast progenitor cells (FPCs) and ROS level in BM after TAC were significantly higher in ALDH2KO mice than in ALDH2 chimeric mice. Furthermore, FPCs were isolated and cultured for in vitro mechanistic studies. The results showed that the stem cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis played a major role in the recruitment of FPCs. In conclusion, our research reveals that increased bone marrow FPCs mobilization and myocardial homing contribute to the enhanced cardiac fibrosis and dysfunction induced by TAC in ALDH2 KO mice via exacerbating accumulation of ROS in BM and myocardial SDF-1 expression.

Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies.

OBJECTIVE: To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). METHOD: A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher-order multiple pregnancies were recruited. Fetal fractions estimated by size ratio-based and Y chromosome-based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. RESULTS: The size ratio-based approach has been well established in estimating fetal fractions for twin and higher-order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%-99.96%) in twins and 97.6% (95% CI, 91.76%-99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. CONCLUSION: Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

Functional and Evolutionary Characterization of the CONSTANS-like Family in Lilium�formolongi.

Lilium�formolongi is a facultative long-day (LD) plant. Aiming to dissect the molecular regulation of the photoperiodic pathway, largely unknown in Lilium, we explored the CONSTANS/FLOWERING LOCUS T (CO/FT) module, a major regulatory factor in the external coincidence model of the photoperiodic flowering pathway in lily. We identified eight CONSTANS-LIKE (COL) family members in L.�formolongi, which could be divided into three types, according to their zinc-finger (B-box) protein domains. Type I included only LfCOL5, containing two B-box motifs. Type II contained six LfCOLs members that had only one B-box motif. Type III contained only LfCOL9 that showed a normal B-box and a second divergent B-box motif. Phylogenic analyses revealed that LfCOL5 was the closest to Arabidopsis CO. LfCOL5, LfCOL6 and LfCOL9 were up-regulated at the flowering induction stage under LDs, coinciding with an increase in LfFT1 expression. LfCOL5, LfCOL6 and LfCOL9 also showed obvious diurnal expression pattern for 3 d under LDs. However, under short-day (SD) conditions, the expression patterns of LfCOL5, LfCOL6 and LfCOL9 were variable and complex, with regard to the developmental stages and circadian rhythm. LfCOL5, LfCOL6 and LfCOL9 complemented the late flowering phenotype of the co mutant in Arabidopsis. Taken together, the results suggest that LfCOL5, LfCOL6 and LfCOL9 are involved in triggering flowering induction under LDs. LfCOL6 and LfCOL9 belong to types different from functional COL homologs in other plant species, illustrating the variation in phylogeny, evolution and gene function among LfCOL family members.

Switching a Perpendicular Ferromagnetic Layer by Competing Spin Currents.

An ultimate goal of spintronics is to control magnetism via electrical means. One promising way is to utilize a current-induced spin-orbit torque (SOT) originating from the strong spin-orbit coupling in heavy metals and their interfaces to switch a single perpendicularly magnetized ferromagnetic layer at room temperature. However, experimental realization of SOT switching to date requires an additional in-plane magnetic field, or other more complex measures, thus severely limiting its prospects. Here we present a novel structure consisting of two heavy metals that delivers competing spin currents of opposite spin indices. Instead of just canceling the pure spin current and the associated SOTs as one expects and corroborated by the widely accepted SOTs, such devices manifest the ability to switch the perpendicular CoFeB magnetization solely with an in-plane current without any magnetic field. Magnetic domain imaging reveals selective asymmetrical domain wall motion under a current. Our discovery not only paves the way for the application of SOT in nonvolatile technologies, but also poses questions on the underlying mechanism of the commonly believed SOT-induced switching phenomenon.

Nontrivial Nature and Penetration Depth of Topological Surface States in SmB_{6} Thin Films.

The nontrivial feature and penetration depth of the topological surface states (TSS) in SmB_{6} were studied via spin pumping. The experiments used SmB_{6} thin films grown on the bulk magnetic insulator Y_{3}Fe_{5}O_{12} (YIG). Upon the excitation of magnetization precession in the YIG, a spin current is generated in the SmB_{6} that produces, via spin-orbit coupling, a lateral electrical voltage in the film. This spin-pumping voltage signal becomes considerably stronger as the temperature decreases from 150 to 10 K, and such an enhancement most likely originates from the spin-momentum locking of the TSS and may thereby serve as evidence for the nontrivial nature of the TSS. The voltage data also show a unique film thickness dependence that suggests a TSS depth of ∼32 nm. The spin-pumping results are supported by transport measurements and analyses using a tight binding model.

Analysis of global gene expression profiles during the flowering initiation process of Lilium × formolongi.

The onset of flowering is critical for the reproductive development of plants. Lilium × formolongi is a lily hybrid that flowers within a year after sowing. We successfully identified four important stages during vegetative growth and flowering initiation of L. × formolongi under long day conditions. The plant tissues from the four stages were used in a genome-wide transcriptional analysis to investigate stage-specific changes of gene expression in L. × formolongi. In total, the sequence reads of the four RNA-sequencing libraries were assembled into 52,824 unigenes, of which 37,031 (70.10%) were differentially expressed. The global expression dynamics of the differentially expressed genes were predominant in flowering induction phase I and the floral differentiation stage, but down-regulated in flowering induction phase II. Various transcription factor families relevant to flowering were elucidated, and the members of the MADS-box, SBP and CO-like transcription factor families were the most represented. There were 85 differentially expressed genes relevant to flowering. CONSTANS-LIKE, FLOWERING LOCUS T, TREHALOSE-6-PHOSPHATE SYNTHASE and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE homologs were discovered and may play significant roles in the flowering induction and transition process of L. × formolongi. A putative gene regulatory network, including photoperiod, age-dependent and trehalose-6-phosphate flowering pathways, was constructed. This is the first expression dataset obtained from a transcriptome analysis of photoperiod-mediated flowering pathway in lily, and it is valuable for the exploration of the molecular mechanisms of flowering initiation and the short vegetative stage of L. × formolongi.

Proteome analysis develops novel plasma proteins classifier in predicting the mortality of COVID-19.

COVID-19 has been a global concern for 3 years, however, consecutive plasma protein changes in the disease course are currently unclear. Setting the mortality within 28 days of admission as the main clinical outcome, plasma samples were collected from patients in discovery and independent validation groups at different time points during the disease course. The whole patients were divided into death and survival groups according to their clinical outcomes. Proteomics and pathway/network analyses were used to find the differentially expressed proteins and pathways. Then, we used machine learning to develop a protein classifier which can predict the clinical outcomes of the patients with COVID-19 and help identify the high-risk patients. Finally, a classifier including C-reactive protein, extracellular matrix protein 1, insulin-like growth factor-binding protein complex acid labile subunit, E3 ubiquitin-protein ligase HECW1 and phosphatidylcholine-sterol acyltransferase was determined. The prediction value of the model was verified with an independent patient cohort. This novel model can realize early prediction of 28-day mortality of patients with COVID-19, with the area under curve 0.88 in discovery group and 0.80 in validation group, superior to 4C mortality and E-CURB65 scores. In total, this work revealed a potential protein classifier which can assist in predicting the outcomes of COVID-19 patients and providing new diagnostic directions.

Critical roles of PAI-1 in lipopolysaccharide-induced acute lung injury.

PURPOSE: Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of fibrinolytic systems. The effect of PAI-1 on inflammatory response is still inconsistent. Our study was conducted to investigate its effects on inflammation to clarify the role of PAI-1 in acute lung injury (ALI) induced by lipopolysaccharide (LPS). MATERIAL AND METHODS: ALI models were established in wild-type (WT) and PAI-1 knockout (KO) mice by LPS intervention for 48 â€‹h. Lung histopathology, wet-dry ratio, total cell count and TNF-α concentration in bronchoalveolar lavage fluid (BALF), and inflammation related proteins were detected. Flow cytometry was used to sort neutrophils, macrophages, regulatory T cells (Treg) and T helper cell 17 (Th17). RNA sequencing was performed to find differentially expressed genes. Masson staining and immunohistochemistry were used to analyze pulmonary fiber deposition and proliferation. RESULTS: Compared with ALI (WT) group, the wet-dry ratio, the total number of BALF cells, the concentration of TNF-α in BALF, and the expression of pp65 in the lung tissue was increased in ALI (PAI-1 KO) group, with increased proportion of neutrophils, decreased proportion of macrophages and decreased proportion of Treg/Th17 in the lung tissue. Collagen fiber deposition and PCNA expression were lighter in ALI (PAI-1 KO) group than ALI (WT) group. PPI analysis showed that PAI-1 was closely related to TNF, IL-6, IL-1ß, Smad2/3 and mainly concentrated in the complement and coagulation system, TNF-α and IL-17 signaling pathways. CONCLUSIONS: PAI-1 KO could aggravate ALI induced by LPS at 48 â€‹h. PAI-1 may be an important target to improve the prognosis of ALI.

Functional analysis of a lily SHORT VEGETATIVE PHASE ortholog in flowering transition and floral development.

Lilium is a commercially important genus of bulbous flowers, investigating the flowering molecular mechanisms is important for flowering regulation of lily. MADS-box SHORT VEGETATIVE PHASE (SVP) orthologs are involved in the flowering transition and floral organ differentiation in many plants. In this study, we identified an SVP ortholog from L. × formolongi (LfSVP), which was closely related to Arabidopsis SVP according to phylogenetic analysis. Tissue-specific expression patterns indicated that LfSVP expression levels peaked in the leaves and showed low expression levels in flowering tepals. Stage-dependent expression patterns of LfSVP showed high transcription level in the flowering induction stage under different photoperiods and exhibited transcription peak in the floral budding development stage under long days. Overexpressed LfSVP led to delayed flowering and floral organ defects in Arabidopsis independent of photoperiod. Tobacco rattle virus -induced gene silencing of LfSVP caused a strongly earlier flowering time and floral organ defects of L. × formolongi. Moreover, LfSVP can interact with L. × formolongi APETALA1 (AP1) in both yeast and tobacco cells, and the two may interact to regulate floral organ differentiation. In conclusion, LfSVP is a flowering repressor and may be involved in the regulation of floral organ differentiation. This study will be helpful for the molecular breeding of short-life-period and rich floral patterns lily varieties.

Robust formation of Skyrmions and topological Hall effect anomaly in epitaxial thin films of MnSi.

Magnetotransport properties have been investigated for epitaxial thin films of B20-type MnSi grown on Si(111) substrates. Lorentz transmission electron microscopy images clearly point to the robust formation of Skyrmions over a wide temperature-magnetic field region. New features distinct from those reported previously for MnSi are observed for epitaxial films: a shorter (nearly half) period of the spin helix and Skyrmions, and a topological Hall effect anomaly consisting in ∼2.2 times enhancement of the amplitude and in the opposite sign with respect to bulk samples.

Inhibition of proteasome, but not lysosome, upregulates organic anion transporter 3 in vitro and in vivo.

Organic anion transporter 3 (OAT3), an indispensable basolateral membrane transporter predominantly distributed in the kidney proximal tubules, mediated the systemic clearance of substrates including clinical drugs, nutrients, endogenous and exogenous metabolites, toxins, and critically sustains body homeostasis. Preliminary data in this study showed that classical proteasome inhibitors (e.g., MG132), but not lysosome inhibitors, significantly increased the OAT3 ubiquitination and OAT3-mediated transport of estrone sulfate (ES) in OAT3 stable expressing cells, indicating that proteasome rather than lysosome is involved in the intracellular fate of OAT3. Next, bortezomib and carfilzomib, two FDA-approved and widely applied anticancer agents through selective targeting proteasome, were further used to define the role of inhibiting proteasome in OAT3 regulation and related molecular mechanisms. The results showed that 20S proteasome activity in cell lysates was suppressed with bortezomib and carfilzomib treatment, leading to the increased OAT3 ubiquitination, stimulated transport activity of ES, enhanced OAT3 surface and total expression. The upregulated OAT3 function by proteasome inhibition was attributed to the augment in maximum transport velocity and stability of membrane OAT3. Lastly, in vivo study using Sprague Dawley rats validated that proteasome inhibition using bortezomib induced enhancement of OAT3 ubiquitination and membrane expression in kidney. These data suggest that activity of proteasome but not lysosome could have an impact on the physiological function of OAT3, and proteasome displayed a promising target for OAT3 regulation in vitro and in vivo, and could be used in restoring OAT3 impairment under pathological conditions, avoiding OAT3-associated toxicity and diseases, ensuring drug efficacy and safety.