Towards energy conservation by constructing more transportation infrastructure?: An endogenous stochastic frontier analysis framework.

Whether constructing more transportation infrastructure can be helpful for the achievement of energy conservation is a long-running and debatable issue. To answer this question, the relationship between transportation infrastructure and energy efficiency must first be clarified. Nonetheless, the existence of the endogeneity problem poses a challenge to defining the relationship. In this paper, an endogenous stochastic frontier analysis method is used to investigate the influence of transportation infrastructure on energy efficiency. Based on the prefecture-city level panel data in China, we find that after addressing the endogeneity problem, the impact of transportation infrastructure on energy efficiency increases dramatically. Moreover, this impact is more pronounced in small-scale cities compared to large and medium-scale cities. Regardless of the measurement of transportation infrastructure, instrumental variable, or production function form, we get the similar conclusions, demonstrating the robustness of our findings. Additional simulation analysis shows that the energy conservation potential would be 1222-2935 million kilowatt hours if the level of transportation infrastructure could be optimized. We recommend accelerating the transportation infrastructure construction, particularly in the small-scale cities so as to boost the energy efficiency and achieve energy conservation targets.

Expression, Prognostic Value, and Functional Mechanism of Polarity-Related Genes in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses around the world. Within-cell polarity is crucial to cell development and function maintenance, and some studies have found that it is closely related to cancer initiation, metastasis, and prognosis. The aim of our research was to find polarity-related biomarkers which improve the treatment and prognosis of HCC. For the knowledge-driven analysis, 189 polarity-related genes (PRGs) were retrieved and curated manually from the molecular signatures database and reviews. Meanwhile, in the data-driven part, genomic datasets and clinical records of HCC was obtained from the cancer genome atlas database. The potential candidates were considered in the respect to differential expression, mutation rate, and prognostic value. Sixty-one PRGs that passed the knowledge and data-driven screening were applied for function analysis and mechanism deduction. Elastic net model combing least absolute shrinkage and selection operator and ridge regression analysis refined the input into a 12-PRG risk model, and its pharmaceutical potency was evaluated. These findings demonstrated that the integration of multi-omics of PRGs can help us in untangling the liver cancer pathogenesis as well as illustrate the underlying mechanisms and therapeutic targets.

Enhanced Sensitivity of Hydrogenated Cu0.27Co2.73O4 Nanooctahedrons Having {111} Facets and the Sensing Mechanism of 3-Coordinated Co/Cu Atoms as Active Centers.

Cu0.27Co2.73O4 nanooctahedrons enclosed by polar {111} planes have been prepared through the selective adsorption of Cl-. Hydrogenation has been successfully used to enhance the responses of the Cu0.27Co2.73O4 nanooctahedron sensors to acetone, ethanol, and n-butylamine. The enhancement of the response results from the increase in the number of 3-coordinated Co/Cu atoms (Co3c/Cu3c) at the (111) plane of Cu0.27Co2.73O4 through removing O-H groups and Cl- ions at the surface by hydrogenation. The Co3c/Cu3c atoms on the (111) plane of Cu0.27Co2.73O4 are considered to function as the gas response active centers. These Co3c/Cu3c active atoms have three functions: generating electrons, adsorbing oxygen from air, and catalyzing the sensing reactions. The hydrogenation polar surface approach can be applied to improve the performances of other sensing materials. Such sensing mechanisms of the Co3c/Cu3c unsaturated atoms as the active centers can be conducive to understanding the gas-sensing essence and the development of sensing materials with high performances.

Comparison of outcomes of peritoneal dialysis between patients after failed kidney transplant and transplant-naïve patients: a meta-analysis of observational studies.

PURPOSE: The influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation. METHODS: We searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR). RESULTS: We included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80-1.61; I2=52%; p = 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97-1.32; I2=5%; p = 0.11] and mortality [RR, 1.00; 95% CI, 0.67-1.50; I2=63%; p = 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88-1.78; I2=79%; p = 0.22], peritonitis [HR, 1.04; 95% CI, 0.72-1.50; I2=76%; p = 0.85] and mortality [HR, 1.24; 95% CI, 0.77-2.00; I2=66%; p = 0.38] between the study groups. CONCLUSION: Patients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.

Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. METHODS: The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs) and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real-time PCR. The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student's t-test or linear regression. Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis. Validation of DELs' functions including proliferation and migration was performed via loss-of-function RNAi assays. RESULTS: In this study, we identified 439 DEGs and 214 DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs, including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition, the co-expression network analysis between DEGs and DELs showed that DELs were involved with metabolic, cell cycle, chemical carcinogenesis, and complement and coagulation cascade-related pathways. The silencing of the endogenous level of NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both SK-HEP-1 and SMMC-7721 HCC cells. CONCLUSION: These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC.

How to promote knowledge transfer within R&D team? An evolutionary game based on prospect theory.

Knowledge transfer is the basis for R&D teams and enterprises to improve innovation performance, win market competition and seek sustainable development. In order to explore the path to promote knowledge transfer within the R&D team, this study considers the bounded rationality and risk preference of individuals, incorporates prospect theory into evolutionary game, constructs a perceived benefits matrix distinct from the traditional benefits matrix, and simulates the evolutionary game process. The results show that, R&D personnel's knowledge transfer decisions depend on the net income difference among strategies; only if perceived cost is less than the sum of perceived synergy benefit, perceived organization reward value, and perceived organization punishment value, can knowledge be fully shared and transferred within the R&D team. Moreover, R&D personnel's knowledge transfer decisions are interfered by the irrational psychological factors, including overconfidence, reflection, loss avoidance, and obsession with small probability events. The findings help R&D teams achieve breakthroughs in improving the efficiency of knowledge transfer, thereby enhancing the capacity of enterprises for collaborative innovation.

Probability of outbreaks and cross-border dissemination of the emerging pathogen: a genomic survey of Elizabethkingia meningoseptica.

IMPORTANCE: Elizabethkingia meningoseptica is an emerging infectious agent associated with life-threatening infections in immunocompromised individuals. However, there are limited data available on the genomic features of E. meningoseptica. This study aims to characterize the geographical distribution, phylogenetic evolution, pathogenesis, and transmission of this bacterium. A systematic analysis of the E. meningoseptica genome revealed that a common ancestor of this bacterium existed 90 years ago. The evolutionary history showed no significant relationship with the sample source, origin, or region, despite the presence of genetic diversity. Whole genome sequencing data also demonstrated that E. meningoseptica bacteria possess inherent resistance and pathogenicity, enabling them to spread within the same hospital and even across borders. This study highlights the potential for E. meningoseptica to cause severe nosocomial outbreaks and horizontal transmission between countries worldwide. The available evidence is crucial for the development of evidence-based public health policies to prevent global outbreaks caused by emerging pathogens.

Small wards in the ICU: a favorable measure for controlling the transmission of carbapenem-resistant Klebsiella pneumoniae.

PURPOSE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the leading causes of healthcare-associated infections (HAIs) and is particularly pervasive in intensive care units (ICUs). This study takes ICU layout as the research object, and integrates clinical data and bacterial genome analysis to clarify the role of separate, small wards within the ICU in controlling the transmission of CRKP. METHODS: This study prospectively observed the carriage and spread of CRKP from a long-term in-hospital patient (hereafter called the Patient) colonized with CRKP in the gut and located in a separate, small ward within the ICU. The study also retrospectively investigated CRKP-HAIs in the same ICU. The relationship and transmission between CRKP isolates from the Patient and HAI events in the ICU were explored with comparative genomics. RESULTS: In this study, 65 CRKP-HAI cases occurred during the investigation period. Seven CRKP-HAI outbreaks were also observed. A total of 95 nonrepetitive CRKP isolates were collected, including 32 strains from the Patient in the separate small ward. Phylogenetic analysis based on core genome single-nucleotide polymorphism (cgSNP) showed that there were five possible CRKP clonal transmission events and two clonal outbreaks (A1, A2) during the study. CRKP strains from the Patient did not cause CRKP between-patient transmission or outbreaks in the ICU during the 5-year study period. CONCLUSION: The presence of a long-term hospitalized patient carrying CRKP and positioned in a separate, small ward did not lead to CRKP transmission or infection outbreaks in the ICU. Combining a small-ward ICU layout with normative HAI control measures for multidrug-resistant pathogen infection was effective in reducing CRKP transmission.

Population genomics of emerging Elizabethkingia anophelis pathogens reveals potential outbreak and rapid global dissemination.

Elizabethkingia anophelis is an emerging species and has increasingly been reported to cause life-threatening infections and even outbreaks in humans. Nevertheless, there is little data regarding the E. anophelis geographical distribution, phylogenetic structure, and transmission across the globe, especially in Asia. We utilize whole-genome sequencing (WGS) data to define a global population framework, phylogenetic structure, geographical distribution, and transmission evaluation of E. anophelis pathogens. The geographical distribution diagram revealed the emerging pathogenic bacteria already distributed in various countries worldwide, especially in the USA and China. Strikingly, phylogenetic analysis showed a part of our China original E. anophelis shared the same ancestor with the USA outbreak strain, which implies the possibility of localized outbreaks and global spread. These closer related strains also contained ICEEaI, which might insert into a disrupted DNA repair mutY gene and made the strain more liable to mutation and outbreak infection. BEAST analysis showed that the most recent common ancestor for ICEEaI E. anophelis was dated twelve years ago, and China might be the most likely recent source of this bacteria. Our study sheds light on the potential possibility of E. anophelis causing the large-scale outbreak and rapid global dissemination. Continued genomic surveillance of the dynamics of E. anophelis populations will generate further knowledge for optimizing future prevent global outbreak infections.

LncNSPL facilitates influenza A viral immune escape by restricting TRIM25-mediated K63-linked RIG-I ubiquitination.

Long noncoding RNAs (lncRNAs) participate in host antiviral responses; however, how viruses exploit host lncRNAs for immune evasion remains largely unexplored. Functional screening of differentially expressed lncRNA profile in patients infected with influenza A virus (IAV) revealed that lncNSPL (Gene Symbol: LOC105370355) was highly expressed in monocytes. Deregulated lncNSPL expression in infected monocytes significantly increased type I interferon (IFN-I) production and inhibited IAV replication. Moreover, lncNSPL overexpression in mice increased the susceptibility to IAV infection and impaired IFN-I production. LncNSPL directly bound to retinoic acid-inducible gene I (RIG-I) and blocked the interaction between RIG-I and E3 ligase tripartite interaction motif 25 (TRIM25), reducing TRIM25-mediated lysine 63 (K63)-linked RIG-I ubiquitination and limiting the downstream production of antiviral mediators during the late stage of IAV infection. Our findings provide mechanistic insights into the means by which lncNSPL promotes IAV replication and immune escape via restricting the TRIM25-mediated RIG-I K63-linked ubiquitination. Thus, lncNSPL may represent a promising pharmaceutical target for anti-IAV therapy.

Effect of alprostadil in the treatment of intensive care unit patients with acute renal injury.

BACKGROUND: Acute kidney injury (AKI) is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen. AIM: To examine the value of alprostadil-assisted continuous venous-venous hemofiltration (CVVH) in the treatment of severe AKI in severely ill patients. METHODS: This was a retrospective study and the inclusion criteria were as follows: (1) Age of patients (≥ 18 years); (2) Admission to intensive care unit due to non-renal primary disease, APACHE II score (≥ 18 points); (3) The diagnostic criteria of AKI guidelines were formulated with reference to the Global Organization for the Improvement of Prognosis in Kidney Diseases, with AKI grades of II-III; (4) All patients were treated with CVVH; and (5) Complete basic data were obtained for all patients. RESULTS: The clinical effect of alprostadil administered in the treatment group was better than that observed in the control group (P < 0.05). The urine output of patients in the alprostadil group returned to normal time (9.1 ± 2.0 d) and was lower than that in the control group (10.6 ± 2.5 d), the difference was statistically significant (P < 0.05); adverse reactions occurred in the alprostadil group compared with the control group, but the difference was not statistically significant (P > 0.05). CONCLUSION: Alprostadil-assisted CVVH in the treatment of severely ill patients with AKI can effectively improve the renal resistance index and partial pressure of urine oxygen, and has a positive effect on improving renal function.

From race-to-the-bottom to strategic imitation: how does political competition impact the environmental enforcement of local governments in China?

In China, national environmental regulations have customarily found themselves to be inhibited by local government's ostensible obedience. This research investigates how local officials, motivated and constrained by political competition, dedicate themselves to the environment and interact with each other regarding environmental regulation implementation and actual regulatory performance. Based on a spatial econometric model using data from 30 provinces from 2000 to 2016, the empirical results document the spatial dependence of environmental regulatory enforcement among provinces of similar economic levels and reveal that since 2007, there has been a performance-oriented peer competition for SO2 emission reduction but no similar competition for CO2 emission reduction. The findings indicate a transformation of the regulatory behavior of local governments from a race-to-the-bottom to strategic imitation and provide institutional insight into the spatial attributes of environmental enforcement under the impact of the political regime in China.

Efficient removal of crystal violet dye using EDTA/graphene oxide functionalized corncob: a novel low cost adsorbent.

In this study, EDTA functionalized corncob (EDTA-corncob) and EDTA/graphene oxide functionalized corncob (EDTA-GO/corncob) were prepared using disodium ethylenediamine tetraacetic acid and the graphene oxide immersion method. EDTA-corncob and EDTA-GO/corncob were characterized by SEM and FTIR spectroscopy. On this basis, the adsorption properties of EDTA-corncob and EDTA-GO/corncob were studied with crystal violet as the adsorbate. The optimum adsorption conditions were determined by the effect of samples on the adsorption properties of crystal violet at different times, temperatures and pH, and the reusability of the samples was studied. The results showed that adsorption capacity of crystal violet on EDTA-GO/corncob was higher compared with natural corncob and EDTA-corncob. The most suitable pH value of the solution is about 6.0, the adsorption equilibrium time is 200 min. EDTA-GO/corncob can be reused eight times. This study indicated that EDTA-GO/corncob is a reusable adsorbent for rapid, low-cost, and efficient removal of dye from waste water.

A novel polyamine-type starch/glycidyl methacrylate copolymer for adsorption of Pb(II), Cu(II), Cd(II) and Cr(III) ions from aqueous solutions.

A novel polyamine-type starch/glycidyl methacrylate (GMA) copolymer with a high capacity for the adsorption of heavy metal ions was prepared via graft copolymerization of GMA and corn starch and a subsequent amination reaction between amino group of diethylenetriamine and epoxy group in GMA. The copolymers were characterized by Fourier transform infrared spectrometry, X-ray diffraction and scanning electron microscopy, and adsorption properties on modified starch of Cu(II), Pb(II), Cd(II) and Cr(III) were studied. By analysing the relationship between adsorption capacity and pH, adsorption isotherms and adsorption kinetics, it is proved that the adsorption of the four metal ions is mainly based on the chemical adsorption of coordination. The maximum adsorption capacities of the copolymer were up to 2.33, 1.25, 0.83 and 0.56 mmol g-1 for Cu(II), Pb(II), Cd(II) and Cr(III), respectively. The adsorption of the four concerned metal ions was hardly affected by common coexisting ions such as Na(I), K(I), Ca(II) and Mg(II), whereas it was slightly decreased when Fe(II) and Zn(II) coexisted in the solution, which illustrates the selective adsorption of Cu(II), Pb(II), Cd(II) and Cr(III) from wastewater. After 10 cycles of adsorption-desorption experiments, there was no significant change in the adsorption capacity, indicating that the polyamine-type starch/GMA copolymer has high adsorption capacity and good reusability.

Draft Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae XPY20 Collected from a Bloodstream Infection Patient.

Bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have been a severe problem with high clinical costs and high mortality rates. The blaKPC-2-producing CRKP strain XPY20 was collected from the blood of a patient. The genome characteristics and antimicrobial resistance mechanisms were determined using next-generation sequencing.

Effect of paiteling on human papillomavirus infection of the cervix.

The aim of the present study was to investigate the effect of the traditional Chinese medicine paiteling on the outcome of high-risk human papillomavirus (HR-HPV) infection of the cervix. A total of 321 patients were enrolled in this study and HPV subtypes were determined by the Hybribio HPV genotyping system. The patients were divided into the loop electrosurgical excision procedure (LEEP; n=82) and non-LEEP (n=239) groups, according to the cervical intraepithelial neoplasia classification. These two groups were further subdivided into the drug (paiteling) and control subgroups. Thin-prep cytology and HR-HPV tests were performed every 3 months for 1 year. In the non-LEEP group, the negative conversion rate of HR-HPV and the regression rate of the cervical lesions in drug subgroup were significantly higher compared with those in the control subgroup. In the LEEP group, the seroconversion rate of the drug subgroup, but not the regression rate of the lesions, was significantly higher compared with that in the control subgroup. The seroconversion rate of HPV16-infected patients at 12 months was 85.7%, whereas it reached 100% in all other HPV subtypes. Therefore, paiteling may accelerate the clearance of HPV infection and the regression of cervical lesions.

[Effect of salpingectomy on ovarian function].

OBJECTIVE: To investigate the effects of salpingectomy on ovarian function. METHODS: Fifty-four women with previous unilateral salpingectomy and 64 with bilateral salpingectomy (study groups) and 59 infertile patients with obstruction of fallopian tube (control group) received in vitro fertilization-embryo transfer (IVF-ET) treatment. The baseline levels of serum FSH, LH, E2, PRL, ovarian response to superovulation and outcome of IVF-ET among the three groups were compared. RESULT: There were no significant differences in the baseline endocrine levels among three groups. There were more ampules and days of gonadotropin (Gn) administration, fewer oocytes retrieved in bilateral salpingectomy group than in control group (P <0.05). The duration of Gn administration of unilateral salpingectomy group was significantly longer than that of control group (P <0.05). The number of oocytes retrieved and the total ampules of Gn administration in unilateral salpingectomy group were not different with those of bilateral salpingectomy group and control group (P >0.05). Among the patients with the history of unilateral salpingectomy, significantly fewer oocytes were retrieved from the ovary on the operated side (P <0.05). There were no significant difference in the fertilization rates, cleavage rates, good-embryo rate, implantation rate, clinical pregnancy rates and good-embryo number among the three groups. CONCLUSION: Salpingectomy has no obvious effect on the outcome of IVF-ET and baseline endocrine within a period of time, but it reduces the ovarian response to superovulation on ipsilateral ovary in IVF-ET.

Identification of Specific Long Non-Coding RNA Expression: Profile and Analysis of Association with Clinicopathologic Characteristics and BRAF Mutation in Papillary Thyroid Cancer.

BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription polymerase chain reaction were used to detect and verify changes to the transcriptome profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathologic characteristics was analyzed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs. Furthermore, the specific subgroup patterns of the PTC transcriptome remodeled by BRAF mutations were also analyzed. RESULTS: A total of 188 lncRNAs and 505 mRNAs were differentially expressed in 50% or more of the PTC tissues (fold change >2; p < 0.05) as assessed by RNA-sequencing compared with paired normal adjacent tissues. Forty-seven lncRNAs and 39 mRNAs were verified in 31 pairs of PTC specimens using quantitative reverse transcription polymerase chain reaction, and the results were consistent with the RNA sequencing data. The lncRNAs NONHSAT076747 and NONHSAT122730 were associated with lymph node metastasis, and NONHSAG051968 expression was negatively correlated with tumor size. A co-expression network between differentially expressed lncRNAs and protein-coding RNAs was constructed and analyzed, and functional analysis suggested that the differentially expressed genes mainly participate in ECM-receptor interactions and the focal adhesion pathway. Furthermore, a specific PTC transcriptome subtype pattern stratified by BRAF mutation was also uncovered. The p53 signaling pathway was the most highly enriched pathway among the BRAF mutation-related genes. CONCLUSIONS: This study reveals specific changes to the lncRNA profile associated with PTC, and provides new insight into its pathogenesis. The PTC-associated lncRNAs NONHSAG051968, NONHSAT076747, and NONHSAT122730 might be potential diagnostic and therapeutic targets for PTC patients, and lncRNAs with subtype-specific expression stratified by BRAF mutation might be significant in individual molecular subtypes.

First report of HGD mutations in a Chinese with alkaptonuria.

Alkaptonuria (AKU) is one of the first prototypic inborn errors in metabolism and the first human disease found to be transmitted via Mendelian autosomal recessive inheritance. It is caused by HGD mutations, which leads to a deficiency in homogentisate 1,2-dioxygenase (HGD) activity. To date, several HGD mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the HGD mutation is very rarely reported. For the Chinese population, no literature on HGD mutation screening is available to date. In this paper, we describe two novel HGD mutations in a Chinese AKU family, the splicing mutation of IVS7+1G>C, a donor splice site of exon 7, and a missense mutation of F329C in exon 12. The predicted new splicing site of the mutated exon 7 sequence demonstrated a 303bp extension after the mutation site. The F329C mutation most probably disturbed the stability of the conformation of the two loops critical to the Fe(2+) active site of the HGD enzyme.

Rapid gene identification in a Chinese osteopetrosis family by whole exome sequencing.

Osteopetrosis is a rare genetically heterogeneous disorder of bone metabolism characterized by increased skeleton density. In the past, standard methods for genetic diagnosis of osteopetrosis have primarily been performed by candidate gene screening and positional cloning. However, these methods are time and labor consumptive; and the genetic basis of approximately 30% of the cases is yet to be elucidated. Here, we employed whole exome sequencing of two affected individuals from an osteopetrosis family to identify a candidate mutation in CLCN7 (Y99C). It was identified from a total of 1757 and 1728 genetic variations found in either patient, which were then distilled using filtering strategies and confirmed using Sanger sequencing. We identified this mutation in six family members, while not in population matched controls. This mutation was previously found in osteopetrosis patients by other researchers. Our evolutionary analysis also indicated that it is under extremely high selective pressure, and is likely to be critical for the correct function of ClC-7, and thus is likely to be the responsible cause of disease. Collectively, our data further indicated that mutation (Y99C) may be a cause of osteopetrosis, and highlights the use of whole exome sequencing as a valuable approach to identifying disease mutations in a cost and time efficient manner.