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"Feng, Kai"
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The 6-4 photoproduct is the trigger of UV-induced replication blockage and ATR activation
The most prevalent human carcinogen is sunlight-associated ultraviolet (UV), a physiologic dose of which generates thousands of DNA lesions per cell, mostly of two types: cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). It has not been possible, in living cells, to precisely characterize the respective contributions of these two lesion types to the signals that regulate cell cycle progression, DNA replication, and cell survival. Here we coupled multiparameter flow cytometry with lesion-specific photolyases that eliminate either CPDs or 6-4PPs and determined their respective contributions to DNA damage responses. Strikingly, only 6-4PP lesions activated the ATR-Chk1 DNA damage response pathway. Mechanistically, 6-4PPs, but not CPDs, impeded DNA replication across the genome as revealed by microfluidic-assisted replication track analysis. Furthermore, single-stranded DNA accumulated preferentially at 6-4PPs during DNA replication, indicating selective and prolonged replication blockage at 6-4PPs. These findings suggest that 6-4PPs, although eightfold fewer in number than CPDs, are the trigger for UV-induced DNA damage responses.
Journal Article
An explanation for the muon and electron g − 2 anomalies and dark matter
A
bstract
We propose simple models with a flavor-dependent global U(1)
ℓ
and a discrete ℤ
2
symmetries to explain the anomalies in the measured anomalous magnetic dipole moments of muon and electron, (
g −
2)
μ,e
, while simultaneously accommodating a dark matter candidate. These new symmetries are introduced not only to avoid the dangerous lepton flavor-violating decays of charged leptons, but also to ensure the stability of the dark matter. Our models can realize the opposite-sign contributions to the muon and electron
g −
2 via one-loop diagrams involving new vector-like leptons. Under the vacuum stability and perturbative unitarity bounds as well as the constraints from the dark matter direct searches and related LHC data, we find suitable parameter space to simultaneously explain (
g −
2)
μ,e
and the relic density. In this parameter space, the coupling of the Higgs boson with muons can be enhanced by up to
∼
38% from its Standard Model value, which can be tested in future collider experiments.
Journal Article
Effect of Helicobacter pylori on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer
ObjectiveGastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection.DesignDeep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H. pylori negative subjects.ResultsIn H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment.Conclusion H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.
Journal Article
The biomechanical effects of treating double-segment lumbar degenerative diseases with unilateral fixation through interlaminar fenestration interbody fusion surgery: a three-dimensional finite element study
Background
Transforaminal lumbar interbody fusion (TLIF) surgery has become increasingly popular in the surgical treatment of lumbar degenerative diseases. The optimal structure for stable double-segment fixation remains unclear.
Objective
To compare the biomechanical changes of unilateral fixation versus bilateral fixation in patients with lumbar degeneration undergoing double-segment TLIF surgery, and to explore the stability and feasibility of unilateral double-segment fixation.
Methods
A three-dimensional finite element model of L3-5 was established based on CT data from a recruited young male volunteer, and the model was validated to have reasonable predictive capability. Surgical procedures were simulated by adjusting bony structures to create models of unilateral and bilateral fixation for double-segment TLIF. Under a pure moment of 10 Nm, range of motion (ROM), extension, lateral bending, axial rotation movements, as well as stresses on interbody fusion devices, internal fixation, and endplates were recorded and compared.
Results
Unilateral fixation was fixed on the left side, with both groups performing flexion, extension, left lateral flexion, right lateral flexion, left rotation, and right rotation movements. All reconstructed conditions showed decreased motion from L3 to L5. Unilateral fixation had greater lumbar spine range of motion (ROM) in all directions compared to bilateral fixation. The greatest difference between the two occurred during right lateral flexion at the L3-4 segment, measuring 1.78°. During right lateral flexion at the L4-5 segment, the largest difference was 2.29°. Regarding stress on the fusion devices, unilateral fixation models exhibited higher stresses than bilateral fixation models, but no significant differences in stability were found. Terminal plate stress in unilateral posterior fixation was higher during flexion than in the bilateral model, showing a similar trend in stress changes. No significant difference was seen in internal fixation stress between the two groups during two-segment fusion, with the posterior internal fixation stress in unilateral fixation being 1.7 times higher during flexion and 1.9 times higher during left bending compared to bilateral fixation.
Conclusion
Unilateral fixation in two-segment transforaminal lumbar interbody fusion (TLIF) surgery can increase stability compared to bilateral fixation, with no significant differences observed between the two models. Unilateral two-segment fixation allows for greater lumbar spine mobility than bilateral fixation, albeit with a slight increase in stress on the posterior fixation and fusion devices under the unilateral fixation mode. This provides some biomechanical evidence for selecting surgical approaches for elderly patients who cannot tolerate long surgeries, suggesting that two-segment unilateral fixation may be advisable.
Clinical trial number
Not applicable.
Journal Article
Birt–Hogg–Dubé syndrome in Chinese patients: a literature review of 120 families
Objective
To clarify the epidemiological and clinical features of Birt–Hogg–Dubé syndrome (BHDS) in Chinese patients.
Methods
We identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2008 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded.
Results
Twenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0 ± 13.9 years (range, 18–84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1–6). The
FLCN
gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%).
Conclusions
Although BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.
Journal Article
A Conceptual Time-Varying Flood Resilience Index for Urban Areas: Munich City
In response to the increased frequency and severity of urban flooding events, flood management strategies are moving away from flood proofing towards flood resilience. The term ‘flood resilience’ has been applied with different definitions. In this paper, it is referred to as the capacity to withstand adverse effects following flooding events and the ability to quickly recover to the original system performance before the event. This paper introduces a novel time-varying Flood Resilience Index (FRI) to quantify the resilience level of households. The introduced FRI includes: (a) Physical indicators from inundation modelling for considering the adverse effects during flooding events, and (b) social and economic indicators for estimating the recovery capacity of the district in returning to the original performance level. The district of Maxvorstadt in Munich city is used for demonstrating the FRI. The time-varying FRI provides a novel insight into indicator-based quantification methods of flood resilience for households in urban areas. It enables a timeline visualization of how a system responds during and after a flooding event.
Journal Article
Interactions Between Commensal Microbiota and Mucosal Immunity in Teleost Fish During Viral Infection With SVCV
The mucosa of vertebrates is a particularly complex but dynamic environment in which the host constantly interacts with trillions of commensal microorganisms and pathogens. Although the internal and external mucosal microbiomes with immune defense of mammals have been well investigated, the relationship between mucosal microbes and their host’s immune responses has not been systematically understood in the early vertebrates. In this study, we compared the composition and distribution of mucosal microbiota in common carp ( Cyprinus carpio ), and found that there were significant differences of microbiota between in the internal (gut) and external mucosal (buccal mucosa, gills and skin) tissues. Next, we successfully constructed an infection model with spring viremia of carp virus (SVCV). Specifically, following viral infection, the immune and antiviral related genes showed different up-regulation in all selected mucosal tissues while significant morphological changes were only found in external tissues including buccal mucosa, gills and skin. Using 16S rRNA gene sequence, we revealed that the abundance of Proteobacteria in mucosal tissues including buccal mucosa, gills and gut showed increased trend after viral infection, whereas the abundance of Fusobacteria significantly decreased in gut. In addition, the loss of dominant commensal microorganisms and increased colonization of opportunistic bacteria were discovered in the mucosal surfaces indicating that a secondary bacterial infection might occur in these mucosal tissues after viral infection. Overall, our results firstly point out the distribution of internal and external mucosal microbiota and analyze the changes of mucosal microbiota in common carp after SVCV infection, which may indicated that the potential role of mucosal microbiota in the antiviral process in early vertebrates.
Journal Article