SERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-type Palmoplantar Keratoderma.

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for NPPK because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. Additionally, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a three-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a 'protease-substrate' manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor, and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in NPPK. These findings may lead to the development of therapeutic strategies for NPPK.

TRPV3-Activated PARP1/AIFM1/MIF Axis through Oxidative Stress Contributes to Atopic Dermatitis.

TRPV3 is a temperature-sensitive calcium-permeable channel. In previous studies, we noticed prominent TUNEL-positive keratinocytes in patients with Olmsted syndrome and Trpv3+/G568V mice, both of which carry gain-of-function variants in the TRPV3 gene. However, it remains unclear how the keratinocytes die and whether this process contributes to more skin disorders. In this study, we showed that gain-of-function variant or pharmacological activation of TRPV3 resulted in poly(ADP-ribose) polymerase 1 (PARP1)/AIFM1/macrophage migration inhibitory factor axis-mediated parthanatos, which is an underestimated form of cell death in skin diseases. Chelating calcium, scavenging ROS, or inhibiting nitric oxide synthase effectively rescued the parthanatos, indicating that TRPV3 regulates parthanatos through calcium-mediated oxidative stress. Furthermore, inhibiting PARP1 downregulated TSLP and IL33 induced by TRPV3 activation in HaCaT cells, reduced immune cell infiltration, and ameliorated epidermal thickening in Trpv3+/G568V mice. Marked parthanatos was also detected in the skin of MC903-treated mice and patients with atopic dermatitis, whereas inhibiting PARP1 largely alleviated the MC903-induced dermatitis. In addition, stimulating parthanatos in mouse skin with methylnitronitrosoguanidine recapitulated many features of atopic dermatitis. These data demonstrate that the TRPV3-regulated parthanatos-associated PARP1/AIFM1/macrophage migration inhibitory factor axis is a critical contributor to the pathogenesis of Olmsted syndrome and atopic dermatitis, suggesting that modulating the PARP1/AIFM1/macrophage migration inhibitory factor axis is a promising therapy for these conditions.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

Isolation and Characterization of the Wastewater Micropollutant Phenacetin-Degrading Bacterium Rhodococcus sp. Strain PNT-23.

Phenacetin, an antipyretic and analgesic drug, poses a serious health risk to both humans and aquatic organisms, which is of concern since this micropollutant is frequently detected in various aquatic environments. However, rare pure bacterial cultures have been reported to degrade phenacetin. Therefore, in this study, the novel phenacetin-degrading strain PNT-23 was isolated from municipal wastewater and identified as a Rhodococcus sp. based on its morphology and 16S rRNA gene sequencing. The isolated strain could completely degrade 100 mg/L phenacetin at an inoculum concentration of OD600 1.5 within 80 h, utilizing the micropollutant as its sole carbon source for growth. Strain PNT-23 exhibited optimal growth in LB medium at 37 °C and a pH of 7.0 with 1% NaCl, while the optimal degradation conditions in minimal medium were 30 °C and a pH of 7.0 with 1% NaCl. Two key intermediates were identified during phenacetin biodegradation by the strain PNT-23: N-acetyl-4-aminophenol and 4-aminophenol. This study provides novel insights into the biodegradation of phenacetin using a pure bacterium culture, expands the known substrate spectra of Rhodococcus strains and presents a potential new candidate for the microbial removal of phenacetin in a diverse range of environments.

Bidirectional Underwater Drag Reduction on Bionic Flounder Two-Tier Structural Surfaces.

Engineering marvels found throughout the exclusive structural features of biological surfaces have given rise to the progressive development of skin friction drag reduction. However, despite many previous works reporting forward drag reduction where the bio-inspired surface features are aligned with the flow direction, it is still challenging to achieve bidirectional drag reduction for non-morphable surface structures. Inspired by the flounder ctenoid scales characterized by tilted, millimeter-sized oval fins embedded with sub-millimeter spikes, we fabricate a bionic flounder two-tier structural surface (BFTSS) that can remarkably reduce the forward skin friction drag by ηdr = 19%. Even in the backwards direction, where the flow is completely against the tilting direction of surface structures, BFTSS still exhibits a considerable drag reduction of ηdr = 4.2%. Experiments and numerical simulations reveal that this unique bidirectional drag reduction is attributed to synergistic effects of the two-tier structures of BFTSS. The array of oval fins can distort the boundary layer flow and mitigate the viscous shear, whilst the microscale spikes act to promote the flow separation to relieve the pressure gradient in the viscous sublayer. Notably, the pressure gradient relief effect of microscale spikes remains invariant to the flow direction and is responsible for the backward drag reduction as well. The bidirectional drag reduction of BFTSS can be extensively applied in minimizing the energy consumption of ships and underwater vessels, as well as in pipeline transport.

Excess KLHL24 Impairs Skin Wound Healing through the Degradation of Vimentin.

Start codon variants in ubiquitin ligase KLHL24 lead to a gain-of-function mutant KLHL24-ΔN28, which mediates the excessive degradation of keratin 15, desmin, and keratin 14, resulting in alopecia, cardiopathy, and epidermolysis bullosa syndrome. Patients with alopecia, cardiopathy, and epidermolysis bullosa syndrome normally present atrophic scars after wounds heal, which is rare in KRT14-related epidermolysis bullosa. The mechanisms underlying the formation of atrophic scars in epidermolysis bullosa of patients with alopecia, cardiopathy, and epidermolysis bullosa syndrome remain unclear. This study showed that KLHL24-ΔN28 impaired skin wound healing by excessively degrading vimentin. Heterozygous Klhl24c.3G>T knock-in mice displayed delayed wound healing and decreased wound collagen deposition. We identified vimentin as an unreported substrate of KLHL24. KLHL24-ΔN28 mediated the excessive degradation of vimentin, which failed to maintain efficient fibroblast proliferation and activation during wound healing. Furthermore, by mediating vimentin degradation, KLHL24 can hinder myofibroblast activation, which attenuated bleomycin-induced skin fibrosis. These findings showed the function of KLHL24 in regulating tissue remodeling, atrophic scarring, and fibrosis.

Investigation of Nagashima-type palmoplantar keratoderma in China: A cross-sectional study of 234 patients.

Nagashima-type palmoplantar keratoderma (NPPK) is the most prevalent hereditary palmoplantar keratoderma (PPK) in China, but there is a paucity of epidemiological data on the Chinese population. To explore the clinical and genetic characteristics, evaluate the demographic distribution, and estimate the burden of disease of NPPK. A total of 234 Chinese patients with NPPK were enrolled from two medical centers and an online PPK support group. Next-generation sequencing and Sanger sequencing were performed to screen out and confirm pathogenic mutations in SERPINB7. Clinical features and quality of life (QOL) were evaluated using self-completed questionnaires. In total, 14 pathogenic mutations were identified in SERPINB7 from the cohort. The top four recurrent mutations were c.796C>T (355, 75.9%), c.522dupT (66, 14.1%), c.650_653delCTGT (24, 5.1%), and c.455G>T (12, 2.6%), accounting for 97.6% of Chinese NPPK patients. Other mutations (11, 2.4%) include c.455-1G>T, c.336+2T>G, c.635delG and seven novel mutations c.2T>C, c.434delG, c.455-16A>G, c.656T>C, c.745-553T>G, c.832C>T, c.1036G>T. The estimated prevalence of NPPK in China was found to be 0.975/10 000 based on Chinese databases. Clinically, there were no apparent genotype-phenotype correlations in NPPK patients. Pediatric patients mainly presented with palmoplantar peeling, while adults presented with scale (p < 0.001). The most common comorbidities in NPPK patients were onychomycosis (40.0%), eczema (36.8%), and tinea pedis (30.3%). As for burden of disease, NPPK patients' QOL was decreased by a moderate degree. In this study, pathogenic mutations' allele frequencies in SERPINB7 were updated, and prevalence of NPPK in China was estimated. This large-scale cohort study provides evidence-based recommendations for patient management. Identification of new mutations are important for timely diagnosis of NPPK. Palmoplantar peeling in children can be used as a hallmark for early recognition of NPPK.

Tiamulin inhibits TNF-α and alleviates psoriasis-like dermatitis.

BACKGROUND: TNF-α elicits a cascade amplification effect in psoriasis. Macromolecule drugs targeting TNF-α are widely used for the clinical treatment of psoriasis. However, there are currently no effective small-molecule inhibitors that can be used in the clinic. OBJECTIVE: Novel TNF-α inhibitor was identified via high-throughput screening (HTS) and its anti-inflammatory activity was evaluated. METHODS: Two cell death models were established to identify inhibitors of TNF-α through HTS from a library of 3256 compounds. The effect of the inhibitor of TNF-α was tested by HaCaT cells in vitro and IMQ-induced psoriasis-like mouse model in vivo. RESULTS: Tiamulin fumarate (TF) was identified as an effective inhibitor of TNF-α. TF significantly blocked the NF-κB and MAPK signaling pathways in TNF-α-stimulated HaCaT cells. Additionally, systemic and topical administration of TF improved IMQ-induced psoriasis-like dermatitis in the mouse model. CONCLUSION: Our study established a HTS method to identify TF as an inhibitor of TNF-α. The protective roles of TF in psoriasis-related inflammation reveal the potential therapeutic value of TF for psoriasis.

Enhancing ink adhesion of specialty paper using an interpenetrating polyvinyl alcohol-blocked polyurethane polymer network sizing system.

The printing quality and strength of specialty papers such as money, maps, newspapers and bank notes have been a significance challenge in recent years. The adhesive effect between ink and paper is depend on both the secondary binding force between the molecules and the mechanical anchoring effect of the ink on the paper. Also, the porous and fibrous structures of base paper restrain its application in printed products because of the strong capillary effect leading to the diffusion of ink particles. To address the problems involved in ink diffusion and mechanical reinforcement, surface sizing is an attractive choice from the perspective of paper handling. Herein, the surface sizing system of specialty paper with an interpenetrating polyvinyl alcohol-blocked polyurethane polymer network was applied to fabricate paper of high ink adhesive properties. In the case of the same external factors (gluing temperature, drying time, etc.), the surface sizing effect of paper samples (sizing with TBPU, polyvinyl alcohol and TBPU/PVA system) were evaluated by infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle measurements and scanning electron microscopy. Some of the pure cotton pulp paper with surface sizing treatment was treated via adhering inks to paper by spraying, smearing and soaking. The bonding strength was tested by peel-off tape tests, soaking tests, and simulated washing tests. The results showed that the water contact angle of the sized-paper increased from 67.6° to 89.7°. The mechanical properties had been greatly improved after treatment and SEM, AFM and XPS analyses indicated an increase in surface roughness and the oxygen-containing polar groups (C[double bond, length as m-dash]O, C-OH, -NH-COO- and COOH) enhanced the fixation of ink particles on the fiber surface. These tests indicated that the novel composite system of TBPU/PVA could endow specialty paper with superb mechanical properties and more than 90% ink retention rate. All these advantages of this composite system may contribute to its wide application in the fields of papermaking and printing.

[Application of continuous renal replacement therapy in infants with acute kidney injury after liver transplantation].

OBJECTIVE: To investigate the clinical application of continuous renal replacement therapy (CRRT) in infants with acute kidney injury (AKI) after liver transplantation. METHODS: A retrospective study was conducted on infants with AKI after liver transplantation in Tianjin First Center Hospital from January 1, 2019 to June 1, 2021. Infants with AKI within 1 year after liver transplantation were divided into CRRT group and non-CRRT group according to whether CRRT was performed. The preoperative and intraoperative condition, the postoperative complications were compared, the risk factors of CRRT for AKI infants, the clinical characteristics of CRRT were analyzed, and the prognosis between CRRT group and non-CRRT group were compared. RESULTS: (1) A total of 512 cases of pediatric liver transplantation were performed. A total of 189 cases (36.9%) developed AKI within 1 year after surgery, including 18 cases in CRRT group and 171 cases in non-CRRT group. (2) There was no significant difference in preoperative conditions between the two groups. The duration of liver transplantation (hours: 8.8±1.5 vs. 7.5±1.3) and intraoperative blood loss [mL: 370 (220-800) vs. 310 (200-400)] in CRRT group were significantly higher than those in non-CRRT group. CRRT group had significantly higher incidence of postoperative complication [unplanned operation: 8 cases (44.4%) vs. 14 cases (8.2%), primary nonfunction: 1 case (5.6%) vs. 0 case (0%), retransplantation: 3 cases (16.7%) vs. 0 case (0%), hepatic artery thrombosis: 3 cases (16.7%) vs. 4 cases (2.3%), intestinal fistula: 2 cases (11.1%) vs. 2 cases (1.2%)] than non-CRRT group (all P < 0.05). (3) The average start time of CRRT was 10 (1-240) days. The per capita frequency of CRRT treatment was 3.3 (1.0-14.0) times. The average duration of each CRRT treatment was 10.1 (6.0-19.3) hours, the average reduction rate of serum creatinine (SCr) was 25.6% (13.5%-45.0%) after CRRT. (4) In CRRT group, 5 patients died, the 1-year and 2-year survival rates were both 72.22%. In non-CRRT group, 6 patients died, the 1-year and 2-year survival rates were 97.1% and 96.5%, respectively. There were significant differences in 1-year and 2-year survival rates between the two groups (both P < 0.01). CONCLUSIONS: The incidence of AKI after pediatric liver transplantation was high, and most infants treated with CRRT were associated with serious surgical complications. CRRT was a powerful means to remove inflammatory factors and maintain the stability of circulation and internal environment, which could improve the multi-organ dysfunction effectively.

Novel and founder variants of SERPINA12 in Chinese patients with autosomal recessive palmoplantar keratoderma.

1. We extend the spectrum of SERPINA12 variants in palmoplantar keratodermas. 2. The recurrent variant c.970_971del, mainly prevalent in the East Asia population, was proved to be a founder variant. 3. Considerable SERPINA12-related palmoplantar keratoderma patients could be identified from autosomal recessive, non-mutilating, diffused palmoplantar keratoderma patients. 4. Other serpin family members or their co-effect may participate in the etiologies of underexplored hereditary palmoplantar keratodermas.

Investigation and Analysis of the Colonization and Prevalence of Carbapenem-Resistant Enterobacteriaceae in Pediatric Liver Transplant Recipients.

OBJECTIVE: This study aimed to investigate the colonization and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in pediatric liver transplant recipients and analyze the high-risk factors and prognosis of CRE infection. METHODS: A prospective study involving 152 pediatric patients undergoing liver transplantation was carried out. Anal swab bacteria cultures were collected when the patients entered the intensive care unit (ICU) and when they left in order to screen for intestinal CRE colonization. The results were grouped according to the occurrence of CRE infection following surgery, and the patients were divided into two groups: a CRE infection group and a non-CRE infection group. Univariate analysis and multiple logistic regression analysis were conducted to determine the independent risk factors of CRE infection and analyze the survival rate. RESULTS: Of the 152 pediatric liver transplant recipients enrolled in the study, there were 13 cases of postoperative CRE infection and 139 cases of non-CRE infection. The incidence of preoperative CRE infection, preoperative cytomegalovirus (CMV) infection, and preoperative sepsis in the CRE infection group was significantly higher than in the non-CRE infection group (P < 0.005). Intraoperative bleeding volume and operation times in the CRE infection group were also significantly higher than in the non-CRE infection group (P < 0.05). Furthermore, postoperative ICU treatment time, postoperative occurrence of unplanned surgery, postoperative mechanical ventilation of more than 24 hours, and the incidence of pre-ICU CRE colonization in the CRE infection group were significantly higher than in the non-CRE infection group (P < 0.05). Finally, the difference between the CRE infection group and the non-CRE infection group in six-month survival rate following surgery was significant (P < 0.001). CONCLUSION: The independent risk factors of CRE infection following pediatric liver transplantation include preoperative CRE infection and pre-ICU CRE colonization. CRE infection progresses quickly, with a poor prognosis and a high mortality rate. The CRE screening of anal swabs is crucial for the early detection of CRE infection.

Near-ideal van der Waals rectifiers based on all-two-dimensional Schottky junctions.

The applications of any two-dimensional (2D) semiconductor devices cannot bypass the control of metal-semiconductor interfaces, which can be severely affected by complex Fermi pinning effects and defect states. Here, we report a near-ideal rectifier in the all-2D Schottky junctions composed of the 2D metal 1 T'-MoTe2 and the semiconducting monolayer MoS2. We show that the van der Waals integration of the two 2D materials can efficiently address the severe Fermi pinning effect generated by conventional metals, leading to increased Schottky barrier height. Furthermore, by healing original atom-vacancies and reducing the intrinsic defect doping in MoS2, the Schottky barrier width can be effectively enlarged by 59%. The 1 T'-MoTe2/healed-MoS2 rectifier exhibits a near-unity ideality factor of ~1.6, a rectifying ratio of >5 × 105, and high external quantum efficiency exceeding 20%. Finally, we generalize the barrier optimization strategy to other Schottky junctions, defining an alternative solution to enhance the performance of 2D-material-based electronic devices.

Hidden Vacancy Benefit in Monolayer 2D Semiconductors.

Monolayer 2D semiconductors (e.g., MoS2 ) are of considerable interest for atomically thin transistors but generally limited by insufficient carrier mobility or driving current. Minimizing the lattice defects in 2D semiconductors represents a common strategy to improve their electronic properties, but has met with limited success to date. Herein, a hidden benefit of the atomic vacancies in monolayer 2D semiconductors to push their performance limit is reported. By purposely tailoring the sulfur vacancies (SVs) to an optimum density of 4.7% in monolayer MoS2 , an unusual mobility enhancement is obtained and a record-high carrier mobility (>115 cm2 V-1 s-1 ) is achieved, realizing monolayer MoS2 transistors with an exceptional current density (>0.60 mA µm-1 ) and a record-high on/off ratio >1010 , and enabling a logic inverter with an ultrahigh voltage gain >100. The systematic transport studies reveal that the counterintuitive vacancy-enhanced transport originates from a nearest-neighbor hopping conduction model, in which an optimum SV density is essential for maximizing the charge hopping probability. Lastly, the vacancy benefit into other monolayer 2D semiconductors is further generalized; thus, a general strategy for tailoring the charge transport properties of monolayer materials is defined.

[Transport Influence and Potential Sources of Ozone Pollution for Nanjing During Spring and Summer in 2017].

In this study, the 24-hour backward trajectories of air mass at ground level(10 m)in Nanjing were calculated by using the HYSPLIT model with the NCEP global reanalysis data from April 1st to October 31st, 2017. The backward trajectories were then combined with the hourly concentration data of O3 in Nanjing for trajectories clustering analysis and potential pollution sources analysis. The results show that in 2017, the maximum daily 8 h running average O3 level in Nanjing was around 12-261 µg·m-3 with 58 days of O3 pollution in Nanjing, mainly in the spring and summer. The monthly variation of O3 showed a single peak, with the highest O3 concentration, as well as the most days exceeding the standard, occurring in June; the diurnal variation of O3 was unimodal and reached its peak around 14:00. A total number of 5136 trajectories were obtained by simulation, among which the exceeded trajectories accounted for approximately 10%. The exceedance trajectories in May and June were significantly higher, accounting for 60% of the total exceedance trajectories. Six ground-level air mass transporting pathways were identified through clustering analysis, from the NNE, NW, SW, SSE, SE, and NE directions. The SE and SSE directions with higher O3 levels were the dominant transport routes of O3 pollution, contributing to 23.33% and 20.76% of backward trajectories, respectively. As for the potential pollution source analysis, the area with high WCWT value distribution matched the WPSCF result, indicating that the potential sources of O3 pollution were mainly distributed in Changzhou, Wuxi, Suzhou, Huzhou, and other cities around Taihu Lake. Additionally, cities located around Nanjing, such as Taizhou, Ma'anshan, Wuhu, Chuzhou, Nantong, and Lianyungang, were considered the secondary potential sources. The results indicate that O3 pollution in Nanjing is a regional issue and its control requires joint prevention and control strategies in the Yangtze River Delta.

Linezolid-induced thrombocytopenia in a child with a liver transplant: A case report.

OBJECTIVE: Linezolid-induced thrombocytopenia is rarely reported in liver transplant patients, especially in children. CASE SUMMARY: We report a case of a 7-month-old liver-transplanted child who suffered from thrombocytopenia induced by linezolid. We simulated the pharmacokinetics of linezolid in a healthy adult using the physiologically based pharmacokinetic (PBPK) model and found that the liver is the most abundant organ for the distribution of linezolid. PRACTICE IMPLICATIONS: Linezolid has a high distribution in the liver. As a result, an increased awareness about the risk of linezolid-induced thrombocytopenia should be strengthened in patients with liver injury. Effects of ethnicity: The differences between Chinese patients and patients of other ethnicities may lead to the diverse effects of linezolid in different patients. The influence of body weight (BW) difference in pharmacokinetics (PK) of linezolid between Asian (Chinese and Japanese) and Caucasians was demonstrated in several population PK studies [1, 2, 3]. The average BW of Asians is lower than that of the Caucasian population, the clearance and apparent volume of distribution are lower than in the European population, and Cmax is higher than in the Western population. Therefore, the adverse effects of linezolid at the same dose may increase in Chinese patients.