Yi Liu’s research while affiliated with The Third Xiangya Hospital of the Central South University and other places

Cervical squamous cell carcinoma (CESC) is one of the most common cancers in women, and radiotherapy has been used as a primary treatment. However, its efficacy is limited by intrinsic and acquired radiation resistance. Our previous study demonstrated that Deoxycytidine kinase (dCK) inhibits ionizing radiation (IR)-induced cell death, including apoptosis and mitotic catastrophe, and dCK is a HSP90-interacting protein by mass spectrometry and co-immunoprecipitation assay. In the present study, we found that dCK inhibited IR-induced ferroptosis by increasing the activity and stability of SLC7A11. Using the E3 ubiquitin ligase database (UbiBrowser), we predicted NEDD4L as a potential ubiquitin ligase of dCK, and WWP1/2 as potential ubiquitin ligases of NEDD4L, respectively. These predictions were subsequently verified through a ubiquitination IP assay. Our findings indicate that HSP90 regulates dCK stability by inhibiting NEDD4L through the recruitment of ubiquitin ligases WWP1/2. In summary, our study reveals the HSP90-WWP1/WWP2-NEDD4L-dCK-SLC7A11 axis as a critical regulator of IR-induced ferroptosis in HeLa cells. These findings provide valuable insights into potential strategies for the radiosensitization of cervical cancer.

Trimethylamine oxide (TMAO) is a newly found intestinal microbiota metabolite. Here, we aimed to explore the effects of TMAO on calcium homeostasis and its implication in cardiac hypertrophy, especially focusing on the regulatory mechanism of TMAO on the key calcium transporter SERCA2a. Echocardiography and histological assessment showed that mice fed with TMAO or Choline for 8 weeks exhibited significant pathological changes of cardiac hypertrophy, which is accompanied by increased plasma levels of TMAO. The results indicated that TMAO could increase the intracellular Ca²⁺ level, up-regulate the expression of ANP and MYH7, and down-regulate SERCA2a expression, which could be reversed by overexpressing of SERCA2a and BAPTA-AM. Meanwhile, TMAO treatment promotes autophagy in vitro and in vivo. By employing immunofluorescence staining and immunoprecipitation assay, it was found that SERCA2a bound to ATG5 and transported to autophagosomes via the ATG5 complex for degradation under TMAO conditions. Furthermore, either 3MA or siATG5 could ameliorate TMAO-induced cardiomyocyte hypertrophy and SERCA2a degradation. Finally, in vivo intervention showed that 3MA could relieve cardiac hypertrophy and rescue the down-regulation of SERCA2a in TMAO-fed mice. The current study identifies a mechanism in which TMAO promotes cardiac hypertrophy via elevated intracellular Ca²⁺ levels and enhanced autophagy degradation of SERCA2a.

Determining the time since deposition (TsD) of body fluid stains can provide crucial criminal information to forensic researchers. Although there are studies on inferring residual time through DNA and RNA markers, this requires high sample quality, and microorganisms, as a new type of marker with individual and tissue identification capabilities, have the potential for body fluid recognition and TsD inference. Blood and semen are the most common types of bodily fluid stains at crime scenes, but research on the inference of the TsD of these two types of stains through microorganisms still needs to be explored. Thus, this study collected samples of body fluid stains exposed indoors for up to 56 days and selected several microorganisms that were both liquid specific and related to residual time inference in blood (Methylobacterium and Sphingomonas) and semen (Gardnerella) stains via 16 S rRNA high-throughput sequencing. Furthermore, the microorganisms’ ability to infer TsD was verified using qPCR in validation group samples stored under the same conditions, and two multiple logistic regression models were constructed. The average absolute deviation of differences between the predicted and actual retention times of the three types of body fluids in the test set using two estimation methods was 2.15 and 2.06 days, respectively. In conclusion, this study has discovered four novel microorganisms related to the retention time of blood and semen and has preliminarily constructed the TsD prediction models, providing a new direction for future forensic research on the inference of TsD in blood and semen stains.

In forensic practice, identifying the species of unknown bodily fluid stains can provide assistance in the qualitative analysis and investigation of cases, and vaginal fluid stains, as one of the common bodily fluid stains, are most commonly seen at the scene of sexual assault. At present, the commonly used vaginal peptidase or microscopic detection methods currently have drawbacks such as high false negative rates, poor sensitivity, and high requirements for sample integrity and background color. However, in forensic investigations, the test materials have specificity and scarcity, making it difficult to ensure their quantity and quality. Thus, in order to achieve rapid and sensitive detection of vaginal fluid stains, in this study, we combined nested PCR and isothermal amplification technology to construct a rapid detection system for suspicious vaginal fluid stains using lateral flow dipstick. This system achieves detection by detecting the specific marker microbial community Lactobacillus crispatus in vaginal fluid, and has a high sensitivity and accuracy, which can achieve detection at template quantities as low as 2.31 copies. More importantly, the system can achieve detection at a constant temperature of 37 °C without the need for complex instruments. It can provide rapid and sensitive identification results, providing assistance for subsequent forensic material extraction and individual identification.

Radiation liver injury is a common complication of hepatocellular carcinoma radiotherapy. It is mainly caused by irreversible damage to the DNA of hepatocellular cells directly by radiation, which seriously interferes with metabolism and causes cell death. AdipoRon can maintain lipid metabolism and stabilize blood sugar by activating adiponectin receptor 1 (AdipoR1). However, the role of AdipoRon/AdipoR1 in the regulation of ionizing radiation (IR)-induced mitochondrial damage remains unclear. In this study, we aimed to elucidate the roles of AdipoRon/AdipoR1 in IR-induced mitochondrial damage in normal hepatocyte cells. We found that AdipoRon treatment rescued IR-induced liver damage in mice and mitochondrial damage in normal hepatocytes in vivo and in vitro. AdipoR1 deficiency exacerbated IR-induced oxidative stress, mitochondrial dynamics, and biogenesis disorder. Mechanistically, the absence of AdipoR1 inhibits the activity of adenosine monophosphate-activated protein kinase α (AMPKα), subsequently leading to disrupted mitochondrial dynamics by decreasing mitofusin (MFN) and increasing dynamin-related protein 1 (DRP1) protein expression. It also controls mitochondrial biogenesis by suppressing the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) and transcription factor A (TFAM) signaling pathway, ultimately resulting in impaired mitochondrial function. To sum up, AdipoRon/AdipoR1 maintain mitochondrial function by regulating mitochondrial dynamics and biogenesis through the AdipoR1-AMPKα signaling pathway. This study reveals the significant role of AdipoR1 in regulating IR-induced mitochondrial damage in hepatocytes and offers a novel approach to protecting against damage caused by IR.

Background Exploring and identifying novel alleles of noncombined DNA Index System (CODIS) short tandem repeat (STR) loci in different ethnic groups is important for the establishment of forensic reference databases and study of population genetics. Aim This study is aimed to explore the genetic polymorphism of 22 non-CODIS autosomal STR loci (D6S477, D18S535, D19S253, D15S659, D11S2368, D20S470, D1S1656, D22-GATA198B05, D8S1132, D4S2366, D21S1270, D13S325, D9S925, D3S3045, D14S608, D10S1435, D12S391, D7S3048, D17S1290, D5S2500, D2S1338, and D16S539) in Sierra Leone population and analyze the population genetic relationships in comparison with other populations. Materials and Methods The samples of a total of 495 unrelated individuals (274 females and 221 males) from Sierra Leone were examined by the Microreader™ 23SP ID System, and their genetic polymorphisms and associated forensic parameters were calculated. The genetic relationships between Sierra Leone population and other populations were evaluated as well. Results A total of 287 alleles were observed with allelic frequencies ranging from 0.001 to 0.399. The cumulative power of discrimination (CPD) of the 22 autosomal STR loci was 0.999999999999999 99999999999999538. The cumulative probability of exclusion (CPE) of the 22 autosomal STR loci was 0.9999998514 (CPEdous) and 0.999999 9999826 (CPEtrios). All of the STR loci reached the Hardy–Weinberg equilibrium after Bonferroni correction. The population genetics analysis results demonstrated that Sierra Leone population exhibited distinctive genetic characteristics compared to those of East Asian populations and it had relatively close genetic distances to the Uygur population. Conclusion The results of this study could enrich the forensic databases with Sierra Leone population. The 22 STR loci are highly polymorphic and could be used for forensic practice and population genetics studies.

Small amounts of DNA from a perpetrator collected during crime-scene investigations can be masked by large amounts of DNA from the victim. These samples can provide important information for the perpetrator’s conviction. Short tandem repeat (STR) detection system is not sensitive enough to detect trace amounts of minor components in unbalanced mixed DNA. We developed a system using droplet digital polymerase chain reaction (ddPCR) capable of discovering trace components and accurately determining the ratio of mixed DNA in extremely unbalanced mixtures. The non-recombining regions of the X chromosome and Y chromosome were quantified in the DNA of male and female mixtures using duplex ddPCR. Absolute quantification of low-abundance portions of trace samples and unbalanced mixtures was done using different mixing ratios. The ddPCR system could be used to detect low-abundance samples with < 5 copies of DNA components in an extremely unbalanced mixture at a mixing ratio of 10000:1. The high sensitivity and specificity of the system could identify the mixing ratio of mixed DNA accurately. A ddPCR system was developed for evaluation of mixed samples of male DNA and female DNA. Our system could detect DNA quantities as low as 5 copies in extremely unbalanced mixed samples with good specificity and applicability. This method could assist forensic investigators in avoiding the omission of important physical evidence, and evaluating the ratio of mixed male/female trace samples.

The PowerPlex® 35GY System (Promega, USA) is an advanced eight-dye multiplex STR kit, incorporating twenty-three autosomal STR loci, eleven Y chromosome STR loci, one sex determining marker Amelogenin, and two quality indicators. This multiplex system includes 20 CODIS loci and up to 15 mini-STR loci with sizing values less than 250 bases. In this study, validation for PowerPlex® 35GY System was conducted following the guidelines of SWGDAM, encompassing sensitivity, precision, accuracy, concordance, species specificity, stutter, mixture, stability, and degraded DNA. The results from experiments demonstrated that the PowerPlex® 35GY System could effectively amplify DNA samples, with complete allele detection achieved at 125 pg. Moreover, over 90% of alleles from minor contributors were detected at a mixed ratio of 1:4. Additionally, the system was found to yield full profiles even in the presence of hematin, humic acid, and indigo. The PowerPlex® 35GY System demonstrated superior performance in the sensitivity and degraded DNA studies compared to a six-dye STR kit. Hence, it is evident that the PowerPlex® 35GY System is well-suited for forensic practice, whether in casework or for database samples. These findings provide strong support for the efficacy and reliability of the PowerPlex® 35GY System in forensic applications.

The spatial equalization of medical facilities can alleviate the wastage of medical resources and improve the efficiency of medical services. Therefore, it is necessary to carry out spatially balanced planning and assessment of medical facilities in cities. Existing studies on the balanced planning, design, and evaluation of medical facilities have been conducted from the perspective of hospital buildings in terms of spatial utilization efficiency, service satisfaction, and their physical environment on one hand, and from the perspective of regional planning of medical facilities in terms of spatial accessibility to medical facilities and the suitability of medical facilities to the social environment on the other hand. This study hopes to break down the boundaries of each perspective and effectively integrate the architecture, planning, and social well-being of medical facilities, taking spatial equilibrium as the core, in order to establish a spatial equilibrium system for medical facilities and achieve a spatial equilibrium-based assessment of the current state of medical facilities. First, the factors influencing the spatial equilibrium of hospital buildings with the support of the system and environment of hospital buildings are determined. Second, the indicators of the spatial equilibrium of hospital buildings are extracted through the consideration of influencing factors, and the indicator weights are determined by discussing the degree to which they contribute to the influence of the operation of hospital building spatial equilibrium systems, thus forming a system of equilibrium indicators for hospital buildings. Finally, a spatial equilibrium evaluation model for hospital buildings is established to assess the effects of equilibrium. The results obtained in this study provide insights into the regional planning of medical facilities and the design of hospital buildings.