Centimetre-scale perovskite solar cells with fill factors of more than 86 per cent.

Owing to rapid development in their efficiency1 and stability2, perovskite solar cells are at the forefront of emerging photovoltaic technologies. State-of-the-art cells exhibit voltage losses3-8 approaching the theoretical minimum and near-unity internal quantum efficiency9-13, but conversion efficiencies are limited by the fill factor (<83%, below the Shockley-Queisser limit of approximately 90%). This limitation results from non-ideal charge transport between the perovskite absorber and the cell's electrodes5,8,13-16. Reducing the electrical series resistance of charge transport layers is therefore crucial for improving efficiency. Here we introduce a reverse-doping process to fabricate nitrogen-doped titanium oxide electron transport layers with outstanding charge transport performance. By incorporating this charge transport material into perovskite solar cells, we demonstrate 1-cm2 cells with fill factors of >86%, and an average fill factor of 85.3%. We also report a certified steady-state efficiency of 22.6% for a 1-cm2 cell (23.33% ± 0.58% from a reverse current-voltage scan).

Elucidating interprotein energy transfer dynamics within the antenna network from purple bacteria.

In photosynthesis, absorbed light energy transfers through a network of antenna proteins with near-unity quantum efficiency to reach the reaction center, which initiates the downstream biochemical reactions. While the energy transfer dynamics within individual antenna proteins have been extensively studied over the past decades, the dynamics between the proteins are poorly understood due to the heterogeneous organization of the network. Previously reported timescales averaged over such heterogeneity, obscuring individual interprotein energy transfer steps. Here, we isolated and interrogated interprotein energy transfer by embedding two variants of the primary antenna protein from purple bacteria, light-harvesting complex 2 (LH2), together into a near-native membrane disc, known as a nanodisc. We integrated ultrafast transient absorption spectroscopy, quantum dynamics simulations, and cryogenic electron microscopy to determine interprotein energy transfer timescales. By varying the diameter of the nanodiscs, we replicated a range of distances between the proteins. The closest distance possible between neighboring LH2, which is the most common in native membranes, is 25 Šand resulted in a timescale of 5.7 ps. Larger distances of 28 to 31 Šresulted in timescales of 10 to 14 ps. Corresponding simulations showed that the fast energy transfer steps between closely spaced LH2 increase transport distances by ∼15%. Overall, our results introduce a framework for well-controlled studies of interprotein energy transfer dynamics and suggest that protein pairs serve as the primary pathway for the efficient transport of solar energy.

Mcrs1 regulates G2/M transition and spindle assembly during mouse oocyte meiosis.

Microspherule protein 1 (Mcrs1) is a component of the nonspecific lethal (NSL) complex and the chromatin remodeling INO80 complex, which participates in transcriptional regulation during mitosis. Here, we investigate the roles of Mcrs1 during female meiosis in mice. We demonstrate that Mcrs1 is a novel regulator of the meiotic G2/M transition and spindle assembly in mouse oocytes. Mcrs1 is present in the nucleus and associates with spindle poles and chromosomes of oocytes during meiosis I. Depletion of Mcrs1 alters HDAC2-mediated H4K16ac, H3K4me2, and H3K9me2 levels in nonsurrounded nucleolus (NSN)-type oocytes, and reduces CDK1 activity and cyclin B1 accumulation, leading to G2/M transition delay. Furthermore, Mcrs1 depletion results in abnormal spindle assembly due to reduced Aurora kinase (Aurka and Aurkc) and Kif2A activities, suggesting that Mcrs1 also plays a transcription-independent role in regulation of metaphase I oocytes. Taken together, our results demonstrate that the transcription factor Mcrs1 has important roles in cell cycle regulation and spindle assembly in mouse oocyte meiosis.

Precise Structural and Dynamical Details in Zeolites Revealed by Coupling-Edited 1H-17O Double Resonance NMR Spectroscopy.

Despite the extensive industrial and research interests in zeolites, their intrinsic catalytic nature is not fully understood due to the complexity of the hydroxyl-aluminum moieties. 17O NMR would provide irreplaceable opportunities for much-needed fine structural determination given the ubiquitous presence of oxygen atoms in nearly all species; however, the low sensitivity and quadrupolar nature of oxygen-17 make its NMR spectroscopic elucidation challenging. Here, we show that state-of-the-art double resonance solid-state NMR techniques have been combined with spectral editing methods based on scalar (through-bond) and dipolar (through-space) couplings, which allowed us to address the subtle protonic structures in zeolites. Notably, the often-neglected and undesired second-order quadrupolar-dipolar cross-term interaction ("2nd-QD interaction") can actually be exploited and can help gain invaluable information. Eventually, a comprehensive set of 1H-17O/1H-27Al double resonance NMR with J-/D-coupling spectral editing techniques have been designed in this work and enabled us to reveal atomic-scale precise structural and dynamical details in zeolites including: 1) The jump rate of the bridging acid site (BAS) proton is relatively low, i.e., far less than 100 s-1 at room temperature. 2) The Al-OH groups with 1H chemical shift at 2.6-2.8 ppm, at least for nonseverely dealuminated H-ZSM-5 catalysts, exhibit a rigid bridging environment similar to that of BAS. 3) The Si-OH groups at 2.0 ppm are not hydrogen bonded and undergo fast cone-rotational motion. The results in this study predict the 2nd-QD interaction to be universal for any rigid -17O-H environment, such as those in metal oxide surfaces or biomaterials.

Nondissociative Activated Dihydrogen Binding on CeO2 Revealed by High-Pressure Operando Solid-State NMR Spectroscopy.

Dihydrogen complexes, which retain the H-H bond, have been extensively studied in molecular science and found to be prevalent in homogeneous and enzymatic catalysis. However, their counterparts in heterogeneous catalysis, specifically nondissociative chemisorbed dihydrogen binding on the catalyst surface, are rarely reported experimentally. This scarcity is due to the complexity of typical material surfaces and the lack of effective characterization techniques to prove and distinguish various dihydrogen binding modes. Herein, using high-pressure operando solid-state NMR technology, we report the first unambiguous experimental observation of activated dihydrogen binding on a reduced ceria catalyst through interactions with surface oxygen vacancies. By employing versatile NMR structural and dynamical analysis methods, we establish a proportional relationship between the degree of ceria surface reduction and dihydrogen binding, as evidenced by NMR observations of H-D through-bond coupling (JHD), T1 relaxation, and proton isotropic chemical shifts. In situ NMR analysis further reveals the participation of bound dihydrogen species in a room-temperature ethylene hydrogenation reaction. The remarkable similarities between surface-activated dihydrogen in heterogeneous catalysis and dihydrogen model molecular complexes can provide valuable insights into the hydrogenation mechanism for many other solid catalysts, potentially enhancing hydrogen utilization.

Sirolimus for kaposiform hemangioendothelioma: Potential mechanisms of action and resistance.

Kaposiform hemangioendotheliomas (KHEs) are vascular tumors that are considered borderline or locally aggressive and may lead to lethal outcomes. Traditional therapies, such as surgery and embolization, may be insufficient or technically impossible for patients with KHE. Sirolimus (or rapamycin), a specific inhibitor of mechanistic target of rapamycin, has recently been demonstrated to be very useful in the treatment of KHEs. Here, we highlight recent substantial progress regarding the effects of sirolimus on KHEs and discuss the potential mechanisms of action of sirolimus in treating this disease. The prevention of platelet activation and inflammation, along with antiangiogenic effects, the inhibition of lymphangiogenesis, the attenuation of fibrosis, or a combination of all these effects, may be responsible for the therapeutic effects of sirolimus. In addition, the mechanism of sirolimus resistance in some KHE patients is discussed. Finally, we review the somatic mutations that have recently been identified in KEH lesions, and discuss the potential of novel therapeutic targets based on these further understandings of the cellular and molecular pathogenesis of KHE.

Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial.

The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 × 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.

Photoinduced Metal-Free Decarboxylative Fluoroalkylation of Alkenes for the Synthesis of N-Arylbutanamides and Oxindoles.

The visible light-induced decarboxylative cascade reaction of fluoroalkyl carboxylic acids has been achieved for the efficient synthesis of fluorinated compounds. However, most of the transformations rely on noble iridium metal complex. Herein, a visible light-induced metal-free decarboxylative cascade reaction of fluoroalkyl carboxylic acids has been realized. This protocol features simple operation, transition metal free, and good functional group tolerance.

Solid-State NMR Dipolar and Chemical Shift Anisotropy Recoupling Techniques for Structural and Dynamical Studies in Biological Systems.

With the development of NMR methodology and technology during the past decades, solid-state NMR (ssNMR) has become a particularly important tool for investigating structure and dynamics at atomic scale in biological systems, where the recoupling techniques play pivotal roles in modern high-resolution MAS NMR. In this review, following a brief introduction on the basic theory of recoupling in ssNMR, we highlight the recent advances in dipolar and chemical shift anisotropy recoupling methods, as well as their applications in structural determination and dynamical characterization at multiple time scales (i.e., fast-, intermediate-, and slow-motion). The performances of these prevalent recoupling techniques are compared and discussed in multiple aspects, together with the representative applications in biomolecules. Given the recent emerging advances in NMR technology, new challenges for recoupling methodology development and potential opportunities for biological systems are also discussed.

Observation-Based Diagnostics of Reactive Nitrogen Recycling through HONO Heterogenous Production: Divergent Implications for Ozone Production and Emission Control.

Understanding of nitrous acid (HONO) production is crucial to photochemical studies, especially in polluted environments like eastern China. In-situ measurements of gaseous and particulate compositions were conducted at a rural coastal site during the 2018 spring Ozone Photochemistry and Export from China Experiment (OPECE). This data set was applied to investigate the recycling of reactive nitrogen through daytime heterogeneous HONO production. Although HONO levels increase during agricultural burning, analysis of the observation data does not indicate more efficient HONO production by agricultural burning aerosols than other anthropogenic aerosols. Box and 1-D modeling analyses reveal the intrinsic relationships between nitrogen dioxide (NO2), particulate nitrate (pNO3), and nitric acid (HNO3), resulting in comparable agreement between observed and simulated HONO concentrations with any one of the three heterogeneous HONO production mechanisms, photosensitized NO2 conversion on aerosols, photolysis of pNO3, and conversion from HNO3. This finding underscores the uncertainties in the mechanistic understanding and quantitative parametrizations of daytime heterogeneous HONO production pathways. Furthermore, the implications for reactive nitrogen recycling, ozone (O3) production, and O3 control strategies vary greatly depending on the HONO production mechanism. On a regional scale, the conversion of HONO from pNO3 can drastically enhance O3 production, while the conversion from NO2 can reduce O3 sensitivity to NOx changes in polluted eastern China.

Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer's disease.

Alzheimer's disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer's disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.

Engineering the Tat-secretion pathway of Bacillus licheniformis for the secretion of cytoplasmic enzyme arginase.

The industrial bacterium Bacillus licheniformis has long been used as a microbial factory for the production of enzymes due to its ability to secrete copious amounts of native extracellular proteins and its generally regarded as safe (GRAS) status. However, most attempts to use B. licheniformis to produce heterologous and cytoplasmic enzymes primarily via the general secretory (Sec) pathway have had limited success. The twin-arginine transport (Tat) pathway offers a promising alternative for the extracellular export of Sec-incompatible proteins because it transports full, correctly folded proteins. However, compared to the Sec pathway, the yields of the Tat pathway have historically been too low for commercial use. To improve the export efficiency of the Tat pathway, we identified the optimal Tat-dependent signal peptides and increased the abundance of the Tat translocases, the signal peptidase (SPase), and the intracellular chaperones. These strategic modifications significantly improved the Tat-dependent secretion of the cytoplasmic enzyme arginase into the culture medium using B. licheniformis. The extracellular enzymatic activity of arginase showed a 5.2-fold increase after these modifications. Moreover, compared to the start strain B. licheniformis 0F3, the production of extracellular GFP was improved by 3.8 times using the strategic modified strain B. licheniformis 0F13, and the extracellular enzymatic activity of SOX had a 1.3-fold increase using the strain B. licheniformis 0F14. This Tat-based production chassis has the potential for enhanced production of Sec-incompatible enzymes, therefore expanding the capability of B. licheniformis as an efficient cellular factory for the production of high-value proteins. KEY POINTS: • Systematic genetic modification of Tat-pathway in B. licheniformis. • Significant enhancement of the secretion capacity of Tat pathway for delivery the cytoplasmic enzyme arginase. • A new platform for efficient extracellular production of Sec-incompatible enzymes.

Sirtuin 3-activated superoxide dismutase 2 mediates fluoride-induced osteoblastic differentiation in vitro and in vivo by down-regulating reactive oxygen species.

Skeletal fluorosis is a chronic metabolic bone disease caused by long-term excessive fluoride intake. Abnormal differentiation of osteoblasts plays an important role in disease progression. Research on the mechanism of fluoride-mediated bone differentiation is necessary for the prevention and treatment of skeletal fluorosis. In the present study, a rat model of fluorosis was established by exposing it to drinking water containing 50 mg/L F-. We found that fluoride promoted Runt-related transcription factor 2 (RUNX2) as well as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) expression in osteoblasts of rat bone tissue. In vitro, we also found that 4 mg/L sodium fluoride promoted osteogenesis-related indicators as well as SOD2 and SIRT3 expression in MG-63 and Saos-2 cells. In addition, we unexpectedly discovered that fluoride suppressed the levels of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) in osteoblasts. When SOD2 or SIRT3 was inhibited in MG-63 cells, fluoride-decreased ROS and mtROS were alleviated, which in turn inhibited fluoride-promoted osteogenic differentiation. In conclusion, our results suggest that SIRT3/SOD2 mediates fluoride-promoted osteoblastic differentiation by down-regulating reactive oxygen species.

Predicting Health Misperceptions: The Role of eHealth Literacy and Situational Perceptions.

This study sought to understand how health misperceptions develop among individuals after exposure to misinformation messages, and how eHealth literacy and situational motivation in problem solving are associated with the negative effects of misinformation exposure. We also sought to understand the differentiated effects of misinformation exposure on the four misinformation-susceptible publics. Results from two studies revealed that situational motivation was positively associated with the formation of misperceptions after misinformation exposure as well as individuals' likelihood of amplifying the misinformation message. However, eHealth literacy does not reduce misperceptions, as had been hypothesized. In fact, eHealth literacy was not significantly associated with misperceptions or with misinformation amplification likelihood. Results also provide support for the typology of misinformation-susceptible publics as misinformation-amplifying publics were the most susceptible to misinformation messages.

Surgical Correction of Orbital Hypertelorism With Absorbable Plate Instead of Frontal and Orbital Bar and Inverted U-Shaped Osteotomy.

OBJECTIVE: The aim of the study is to investigate the effect and feasibility of using absorbable plate instead of frontal and orbital bar and inverted U-shaped osteotomy to correct the widening of orbital distance. METHODS: The surgical effect and feasibility of using absorbable plate instead of frontal and orbital bridge plus inverted U-osteotomy for orbital widening syndrome in seven cases between January 2019 and February 2022 were retrospectively analyzed. First, the surgical procedure for orbital hypertelorism was inverted U-shaped orbital osteotomy, and a frontal bone flap was removed, exposing the superior orbital margin and the orbital circumference, and the orbital bone was directly cut off by inverted U-shaped osteotomy. The widened bone in the middle of the orbit was removed, and a long absorbable plate was used to replace the orbitofrontal bridge. The two sides of the orbit were fixed on the absorbable plate, and the absorbable plate was fixed on the rear skull. The clinical effect of treatment, complications (such as cerebrospinal fluid leakage and infection), safety, and feasibility of surgery were evaluated. RESULTS: Using absorbable plate instead of fronto-orbital bridge achieved the effect of orbitofrontal bridge, without orbital distance widening, cerebrospinal fluid leakage, and intracranial infection. Operating time was reduced. There was no metal fixation, and there was no risk of a second operation. CONCLUSIONS: The effect of replacing the frontal-orbital bridge with an absorbable plate and inverted U-shaped osteotomy is positive, the operation time is short, and the orbital distance is clearly improved. This approach can replace the traditional orbital-distance operation, and the incidence of postoperative cerebrospinal fluid leakage and infection is low. Long-term follow-up results are stable.

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single-cell RNA sequencing.

Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome-wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, ß-receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse-variance-weighted method. Mendelian randomization analysis showed that BBs with the ß1-adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267-0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422-0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single-cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1-targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

Impact of Anterior and Posterior Vault Distraction Osteogenesis (A-PVDO) and 3D-Printed Positioning/Shaping Templates in Apert Syndrome: A Case Series Study.

OBJECTIVE: This study seeks to examine the impact of anterior and posterior vault distraction osteogenesis (A-PVDO) in conjunction with 3D-printed positioning and shaping templates for the management of Apert syndrome. METHODS: From January 2018 to February 2022, a retrospective analysis was conducted on 6 cases of Apert syndrome employing fronto-orbital 3D-printed positioning and molding templates. The cranium underwent surgical modification in accordance with the template's configuration and was affixed with absorbable plates. Subsequently, distraction devices were applied, encompassing both anterior and posterior craniotomies. The evaluation encompassed clinical outcomes, complications (including cerebrospinal fluid leakage and infection), safety, and the feasibility of the distraction osteogenesis procedure. RESULTS: Six patients diagnosed with Apert syndrome underwent treatment involving the integration of fronto-orbital 3D-printed positioning and shaping templates in conjunction with anterior and posterior cranial distraction osteoplasty. Follow-up durations ranged from 18 to 32 months (average: 22 mo). No instances of fronto-orbital retraction, cerebrospinal fluid leakage, or intracranial infection were noted during the follow-up period. The sole reported complication entailed an infection at the extension rod site in 1 case. All patients conveyed satisfaction with the treatment outcomes. CONCLUSIONS: The application of 3D-printed positioning and shaping templates in tandem with anterior and posterior cranial distraction osteogenesis demonstrates efficacy in addressing Apert syndrome. Notably, significant enhancements in head shape and orbit were observed, and the incidence of postoperative complications such as cerebrospinal fluid leakage and infection remained minimal. Moreover, long-term follow-up affirmed stability.

The role of neutrophil and LDL-C levels in predicting intracranial hemorrhage following endovascular thrombectomy in patients with acute ischemic stroke.

OBJECTIVES: To investigate the association between intracranial hemorrhage (ICH) and preoperative levels of neutrophils and low-density lipoprotein-cholesterol (LDL-C) in acute ischemic stroke (AIS) patients following endovascular thrombectomy (EVT), and to assess the predictive value of preoperative levels of neutrophils and LDL-C. METHODS: A retrospective analysis was performed on the clinical records of patients diagnosed with AIS who underwent EVT at Nanchong Central Hospital between 2019 and 2023. Multivariate regression analysis was employed to examine the association of preoperative levels of neutrophils and LDL-C with the occurrence of ICH. Furthermore, a receiver operating characteristic curve was constructed to assess the predictive efficacy of these parameters. RESULTS: A total of 300 patients with a mean age of 68.0 years (standard deviation, 11.1 years) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 15.5 (interquartile range, 12.0-19.75) were identified in this cohort. Of these, 28 (9.3%) patients experienced ICH. Multivariate regression analysis revealed that elevated preoperative neutrophil (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.10-1.38, P < 0.001) and LDL-C (OR 2.64, 95% CI 1.52-4.58, P < 0.001) levels were independently associated with ICH. The combined indicator demonstrated a higher area under the curve (AUC 0.759, 95% CI 0.654-0.865) compared with preoperative neutrophil (AUC 0.647, 95% CI 0.532-0.763) and LDL-C (AUC 0.711, 95% CI 0.607-0.814) levels individually.The specificity and sensitivity of the combined indicator were 67.9% and 83.1%, respectively. CONCLUSIONS: Preoperative levels of neutrophils and LDL-C may serve as predictive indicators for ICH in patients with AIS who have undergone EVT; moreover, the combination of preoperative neutrophil and LDL-C levels demonstrates enhanced predictive efficacy.

Association between mtDNA haplogroups and skeletal fluorosis in Han population residing in drinking water endemic fluorosis area of northern China.

To investigate the association between mtDNA genetic information and the risk of SF, individuals were conducted in the drinking water endemic fluorosis area in northern China, sequenced the whole genome of mtDNA, identified the SNPs and SNVs, analyzed the haplogroups, and diagnosed SF, and then, the effect of mtDNA genetic information on the risk of SF was evaluated. We find that, D5 haplogroup and its specific SNPs reduced the risk, while the D4 haplogroup and its specific SNPs increased the risk of SF. The number of SNVs in coding regions of mitochondrial respiratory chain (MRC) is different between the controls and cases. This suggests that D5 haplogroup may play a protective role in the risk of SF, while the opposite is observed for the D4 haplogroup, this may relate to their specific SNPs. And SNVs that encode the MRC complex may also be associated with the risk of SF.

LDL receptor-related protein 5 rs648438 polymorphism is associated with the risk of skeletal fluorosis.

To investigate the potential association between LRP5 rs648438 polymorphism and the risk of skeletal fluorosis (SF) was evaluated in a cross-sectional case-control study conducted in Shanxi, China, in 2019. A total of 973 individuals were enrolled in this study, in which cases and controls were 346 and 627, respectively. SF was diagnosed according to the standard WS/192-2008 (China). The LRP5 rs648438 was detected by the multiple PCR and sequencing. LRP5 rs648438 was found to follow a dominant genetic model using a web-based SNP-STATS software. Logistic regression analysis found that the TC/CC genotype of LRP5 rs648438 might be a protective factor for SF. When stratified by gender, this protective effect of TC/CC genotype in rs648438 was pronounced in males. There was an interaction between gender and rs648438 on risk of SF. Our study suggested that TC/CC genotype of rs648438 might be a protective factor for water-drinking-type skeletal fluorosis, especially in male participants.