SZC010 suppresses breast cancer development by regulating the PI3K/Akt/NF-κB signaling pathway.

BACKGROUND: Breast cancer has become one of the leading causes of cancer deaths and is the most frequently diagnosed cancer among females worldwide. Despite advances in breast cancer therapy, metastatic disease in most patients will eventually progress due to the development of de novo or secondary resistance. Thus, it is extremely important to seek novel drugs with high effectiveness and low toxicity for systematic therapy. METHODS: We applied a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in this study to analyze and evaluate the cytotoxic activity of oleanolic acid (OA) and its derivatives in three types of breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-453). A flow cytometry assay was performed to access the mechanisms of apoptosis and cell cycle analysis in SZC010 in MDA-MB-453 cells. Apoptosis- and cyclin-related proteins were evaluated by western blot. The key proteins of the NF-κB and PI3K-Akt-mTOR signaling pathway were also evaluated by western blot. RESULTS: Our results revealed that all OA derivatives were more effective than OA in three types of breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-453). Among these seven OA derivatives, SZC010 exhibited the most potent cytotoxicity in MDA-MB-453 cells. Additionally, we observed that SZC010 treatment induced dose-and time-dependent growth inhibition in MDA-MB-453 cells. Furthermore, we demonstrated that SZC010 induced growth arrest in the G2/M phase and apoptosis by inhibition of NF-κB activation via the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Our data indicate that the novel OA derivative, SZC010, has great potential in breast cancer therapy.

Carbon Nanotubes as a Solid-State Electron Mediator for Visible-Light-Driven Z-Scheme Overall Water Splitting.

So-called Z-scheme systems, which typically comprise an H2 evolution photocatalyst (HEP), an O2 evolution photocatalyst (OEP), and an electron mediator, represent a promising approach to solar hydrogen production via photocatalytic overall water splitting (OWS). The electron mediator transferring photogenerated charges between the HEP and OEP governs the performance of such systems. However, existing electron mediators suffer from low stability, corrosiveness to the photocatalysts, and parasitic light absorption. In the present work, carbon nanotubes (CNTs) were shown to function as an effective solid-state electron mediator in a Z-scheme OWS system. Based on the high stability and good charge transfer characteristics of CNTs, this system exhibited superior OWS performance compared with other systems using more common electron mediators. The as-constructed system evolved stoichiometric amounts of H2 and O2 at near-ambient pressure with a solar-to-hydrogen energy conversion efficiency of 0.15%. The OWS reaction was also promoted in the case that this CNT-based Z-scheme system was immobilized on a substrate. Hence, CNTs are a viable electron mediator material for large-scale Z-scheme OWS systems.

Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method.

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.

The threaten of typhoons to the health of residents in inland areas: a study on the vulnerability of residents to death risk during typhoon "Lekima" : In Jinan, China.

BACKGROUND: Studies had suggested increased risk of death of residents was associated with typhoons, particularly coastal regions. However, these findings ignored the impact of inland typhoons on the health of residents, especially the indirect death risk caused by typhoons. This study aimed to investigate the acute death risk of residents during inland typhoon Lekima in Jinan, further identify vulnerable populations and areas. METHODS: We selected the daily death from 11 to 27th August 2019 in Jinan as case period, and conducted a time-stratified case-crossover design to match the contemporaneous data from 2016 to 2018 as control period. We used the generalized linear Poisson models to estimate the related effects of death risk during typhoon Lekima and lag days. RESULTS: During the Lekima typhoon month, there were 3,366 deaths occurred in Jinan. Compared to unexposed periods, the acute death risk of non-accidental diseases (especially circulatory diseases), female and the older adults increased significantly in the second week after the typhoon. The maximum significant effect of circulatory disease deaths, female and older adult deaths were appeared on lag9, lag9, and lag13 respectively. And the typhoon-associated RR were 1.19 (95%CI:1.05,1.34), 1.28 (95%CI:1.08,1.52), and 1.22 (95%CI:1.06,1.42) respectively. The acute death risk of residents living in TQ and CQ increased significantly on Lag2 and Lag6 after the typhoon, respectively, while those living in LX, LC, HY, JY, and SH occurred from Lag 8 to Lag 13 after the typhoon. LC lasted the longest days. CONCLUSIONS: Typhoons would increase the vulnerability of residents living in Jinan which mainly occurred from the seventh day after the typhoon. Residents suffering from non-accidental diseases (circulatory diseases), female and the older adults were more vulnerable. The vulnerability of TQ and CQ occurred on Lag2 and Lag6 after typhoon Lekima, respectively, and the other areas except ZQ and PY occurred from Lag 8 to Lag 13. LC lasted the longest duration. Our findings emphasized the importance of the emergency response, which would help policymakers to identify vulnerable regions and populations accurately during typhoons and formulate the emergency response plan.

Efficient and stable visible-light-driven Z-scheme overall water splitting using an oxysulfide H2 evolution photocatalyst.

So-called Z-scheme systems permit overall water splitting using narrow-bandgap photocatalysts. To boost the performance of such systems, it is necessary to enhance the intrinsic activities of the hydrogen evolution photocatalyst and oxygen evolution photocatalyst, promote electron transfer from the oxygen evolution photocatalyst to the hydrogen evolution photocatalyst, and suppress back reactions. The present work develop a high-performance oxysulfide photocatalyst, Sm2Ti2O5S2, as an hydrogen evolution photocatalyst for use in a Z-scheme overall water splitting system in combination with BiVO4 as the oxygen evolution photocatalyst and reduced graphene oxide as the solid-state electron mediator. After surface modifications of the photocatalysts to promote charge separation and redox reactions, this system is able to split water into hydrogen and oxygen for more than 100 hours with a solar-to-hydrogen energy conversion efficiency of 0.22%. In contrast to many existing photocatalytic systems, the water splitting activity of the present system is only minimally reduced by increasing the background pressure to 90 kPa. These results suggest characteristics suitable for applications under practical operating conditions.

Flux-Assisted Synthesis of Y2 Ti2 O5 S2 for Photocatalytic Hydrogen and Oxygen Evolution Reactions.

Photocatalytic water splitting is an ideal means of producing hydrogen in a sustainable manner, and developing highly efficient photocatalysts is a vital aspect of realizing this process. The photocatalyst Y2 Ti2 O5 S2 (YTOS) is capable of absorbing at wavelengths up to 650 nm and exhibits outstanding thermal and chemical durability compared with other oxysulfides. However, the photocatalytic performance of YTOS synthesized using the conventional solid-state reaction (SSR) process is limited owing to the large particle sizes and structural defects associated with this synthetic method. Herein, we report the synthesis of YTOS particles by a flux-assisted technique. The enhanced mass transfer efficiency in the flux significantly reduced the preparation time compared with the SSR method. In addition, the resulting YTOS showed improved photocatalytic H2 and O2 evolution activity when loaded with Rh and Co3 O4 co-catalysts, respectively. These improvements are attributed to the reduced particle size and enhanced crystallinity of the material as well as the slower decay of photogenerated carriers on a nanosecond to sub-microsecond time range. Further optimization of this flux-assisted method together with suitable surface modification is expected to produce high-quality YTOS crystals with superior photocatalytic activity.

Pb-rich Cu grain boundary sites for selective CO-to-n-propanol electroconversion.

Electrochemical carbon monoxide (CO) reduction to high-energy-density fuels provides a potential way for chemical production and intermittent energy storage. As a valuable C3 species, n-propanol still suffers from a relatively low Faradaic efficiency (FE), sluggish conversion rate and poor stability. Herein, we introduce an "atomic size misfit" strategy to modulate active sites, and report a facile synthesis of a Pb-doped Cu catalyst with numerous atomic Pb-concentrated grain boundaries. Operando spectroscopy studies demonstrate that these Pb-rich Cu-grain boundary sites exhibit stable low coordination and can achieve a stronger CO adsorption for a higher surface CO coverage. Using this Pb-Cu catalyst, we achieve a CO-to-n-propanol FE (FEpropanol) of 47 ± 3% and a half-cell energy conversion efficiency (EE) of 25% in a flow cell. When applied in a membrane electrode assembly (MEA) device, a stable FEpropanol above 30% and the corresponding full-cell EE of over 16% are maintained for over 100 h with the n-propanol partial current above 300 mA (5 cm2 electrode). Furthermore, operando X-ray absorption spectroscopy and theoretical studies reveal that the structurally-flexible Pb-Cu surface can adaptively stabilize the key intermediates, which strengthens the *CO binding while maintaining the C-C coupling ability, thus promoting the CO-to-n-propanol conversion.

SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway.

Macrophages preferentially polarize to the anti-inflammatory M2 subtype in response to alterations in the wound microenvironment. SUMO-specific protease 3 (SENP3), a SUMO-specific protease, has been proven to regulate inflammation in macrophages by deSUMOylating substrate proteins, but its contribution to wound healing is poorly defined. Here, we report that SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing in macrophage-specific SENP3 knockout mice. Notably, it affects wound healing through the suppression of inflammation and promotion of angiogenesis and collagen remodeling. Mechanistically, we identified that SENP3 knockout facilitates M2 polarization through the Smad6/IκB/p65 signaling pathway. SENP3 knockout elevated the expression of Smad6 and IκB. Moreover, Smad6 silencing enhanced the expression of p-p65 and proinflammatory cytokines while inhibiting the level of IκB. Our study revealed the essential role of SENP3 in M2 polarization and wound healing, which offers a theoretical basis for further research and a therapeutic strategy for wound healing.

Quantifying the effects of cold waves on carbon monoxide poisoning: A time-stratified case-crossover study in Jinan, China.

Background: Previous studies have shown that carbon monoxide (CO) poisoning occurs mostly in winter and is associated with severe cold weather (e.g., ice storms, temperature drops). However, according to previous studies, the impact of low temperature on health has a delayed effect, and the existing research cannot fully reveal the delayed effect of cold waves on CO poisoning. Objectives: The purpose of this study is to analyze the temporal distribution of CO poisoning in Jinan and to explore the acute effect of cold waves on CO poisoning. Methods: We collected emergency call data for CO poisoning in Jinan from 2013 to 2020 and used a time-stratified case-crossover design combined with a conditional logistic regression model to evaluate the impact of the cold wave day and lag 0-8 days on CO poisoning. In addition, 10 definitions of a cold wave were considered to evaluate the impact of different temperature thresholds and durations. Results: During the study period, a total of 1,387 cases of CO poisoning in Jinan used the emergency call system, and more than 85% occurred in cold months. Our findings suggest that cold waves are associated with an increased risk of CO poisoning in Jinan. When P01, P05, and P10 (P01, P05, and P10 refer to the 1st, 5th, and 10th percentiles of the lowest temperature, respectively) were used as temperature thresholds for cold waves, the most significant effects (the maximum OR value, which refers to the risk of CO poisoning on cold wave days compared to other days) were 2.53 (95% CI:1.54, 4.16), 2.06 (95% CI:1.57, 2.7), and 1.49 (95% CI:1.27, 1.74), respectively. Conclusion: Cold waves are associated with an increased risk of CO poisoning, and the risk increases with lower temperature thresholds and longer cold wave durations. Cold wave warnings should be issued and corresponding protective policies should be formulated to reduce the potential risk of CO poisoning.

A perspective on two pathways of photocatalytic water splitting and their practical application systems.

Photocatalytic water splitting has been widely studied as a means of converting solar energy into hydrogen as an ideal energy carrier in the future. Systems for photocatalytic water splitting can be divided into one-step excitation and two-step excitation processes. The former uses a single photocatalyst while the latter uses a pair of photocatalysts to separately generate hydrogen and oxygen. Significant progress has been made in each type of photocatalytic water splitting system in recent years, although improving the solar-to-hydrogen energy conversion efficiency and constructing practical technologies remain important tasks. This perspective summarizes recent advances in the field of photocatalytic overall water splitting, with a focus on the design of photocatalysts, co-catalysts and reaction systems. The associated challenges and potential approaches to practical solar hydrogen production via photocatalytic water splitting are also presented.

Overall Water Splitting by a SrTaO2N-Based Photocatalyst Decorated with an Ir-Promoted Ru-Based Cocatalyst.

The development of narrow-bandgap photocatalysts for one-step-excitation overall water splitting (OWS) remains a critical challenge in the field of solar hydrogen production. SrTaO2N is a photocatalytic material having a band structure suitable for OWS under visible light (λ ≤ 600 nm). However, the presence of defects in the oxynitride and the lack of cocatalysts to promote simultaneous hydrogen and oxygen evolution make it challenging to realize OWS using this material. The present work demonstrates a SrTaO2N-based particulate photocatalyst for OWS. This photocatalyst, which was composed of single crystals, was obtained by nitriding SrCl2 and Ta2O5 together with NaOH, with the latter added to control the formation of defects. The subsequent loading of bimetallic RuIrOx nanoparticles accelerated charge separation and allowed the SrTaO2N photocatalyst to exhibit superior OWS activity. This research presenting the strategies of controlling the oxygen sources and promoting the cocatalyst function is expected to expand the range of potential OWS-active oxynitride photocatalysts and permit the design of efficient cocatalysts for photocatalytic OWS.

Breast cancer brain metastasis: Current evidence and future directions.

Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths after lung cancer. Metastasis of the central nervous system is a terrible event for breast cancer patients, affecting their survival and quality of life. Compared with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients, brain metastases are more likely to affect patients with triple-negative breast cancer and human epidermal growth factor receptor 2-positive breast cancer. The treatment of breast cancer has improved greatly in the last two decades. However, brain metastases from breast cancer remain the leading cause of morbidity and mortality. Patients with breast cancer brain metastasis have been in an inferior position due to the lack of clinical research in this field, and they are often explicitly excluded from almost all clinical trials. The occurrence and progression of brain metastases will result in severe cognitive impairment and adverse physical consequences, so we must have a good understanding of the molecular mechanisms of breast cancer brain metastasis. In this article, we have retrieved the latest literature of molecules and pathways associated with breast cancer brain metastasis, summarized common therapy strategies, and discussed the prospects and clinical implications of targeting the molecules involved.

Clinical study on the treatment of primary trigeminal neuralgia by robot-assisted percutaneous balloon compression.

Background: C-arm-guided percutaneous puncture balloon compression alone has risk factors of puncture failure, complications, and poor prognosis. Robot-assisted PBC can effectively increase the one-time puncture success rate and improve the safety of the procedure. However, evidence on the superiority of robot-assisted PBC over C-arm-guided PBC alone remains relatively limited. Methods: Retrospective analysis The clinical data of 60 patients with trigeminal neuralgia aged 60 years or older in the Department of Neurosurgery of the Fourth Hospital of Harbin Medical University from January 2021 to October 2021. There were 29 males and 31 females, and the patients' ages ranged from 60 to 79 years, with an average of 71.63 ± 5.12 years. Two groups were divided according to the surgical method, the C-arm guidance-only group (30 cases, n = 30) and the robot-assisted group (30 cases, n = 30). The success rate of first puncture, total operation time, number of "pear-shaped" balloons, number of C-arm x-ray scans, and immediate postoperative relief rate were recorded in both groups, and follow-up was performed to evaluate the postoperative results and complications. The overall evaluation of postoperative results and complications was performed. Results: Intraoperative balloon compression was successfully completed in all 60 patients, and the first puncture success rate was higher in the robot-assisted group than in the simple C-arm group, with a significant difference between the two groups (P < 0.001). In terms of intraoperative balloon morphology, the number of "pear-shaped" balloons was higher in the PBC than in the C-arm-only PBC group, with a significant difference between the two groups (P < 0.005). The degree of immediate postoperative remission in the robotic group was 0 VAS score, which was not statistically significant in both groups (P > 0.05). By the final follow-up, the mean VAS score of the robot-assisted group was lower than that of the simple C-arm group, and both were statistically significant (P < 0.05); complications of masticatory muscle weakness or abnormal facial sensation occurred in both groups after surgery, but the number of cases in the robot-assisted group was less than that of the simple C-arm group. Conclusion: Robot-assisted PBC is better than PBC with a C-arm x-ray machine in terms of first puncture success rate, number of intraoperative balloon "pear-shaped" cases, number of C-arm x-ray scans and short-term efficacy.

In situ Cu single atoms anchoring on MOF-derived porous TiO2 for the efficient separation of photon-generated carriers and photocatalytic H2 evolution.

Single atom catalysts (SACs) have an extremely high atom utilization and distinctive structures and properties in the field of photocatalysis. However, the premise of conducting scientific research and applications is still the stability and catalytic activity of single atoms on suitable substrates. Metal organic frameworks (MOFs), as one of the most suitable single-atom substrates, have tunable internal structures, unsaturated coordination bonds, and high specific surface areas. In this work, Ti-based MOF, MIL-125, was adopted as the precursor to prepare mesoporous Cu-loaded TiO2. During the synthesis of MIL-125, a Cu source was added, and Cu atoms were fixed by partly replacing Ti atoms in the Ti-O octahedron to coordinate with O atoms, resulting in a good dispersity, good stability and high loading amount. Experimental investigations demonstrated that dispersed Cu single atoms act as reaction centres, besides being able to accelerate the transfer of photoelectrons. Under simulated sunlight, the H2 evolution rate of the optimum Cu-TiO2 sample reaches 17.77 mmol g-1 h-1, nearly 101 times higher than that of the pure mesoporous TiO2. The apparent quantum efficiency (AQE) is 20.15% under 365 nm irradiation. This research opens a new thinking to preparing high stability and high activity single atom photocatalysts.

Combined multi-scale mesh and full-matrix inversion for enhancing time-domain breast diffuse optical tomography.

Time-domain diffuse optical tomography can efficiently reconstruct both absorption and reduced scattering coefficients but is heavily limited by the ill-posedness in its inverse problem and low spatial resolution. To deal with these adversities, the truncated singular value decomposition (TSVD)-based whole-weighting-matrix inversion scheme can be a particularly suitable implementation. Unfortunately, TSVD is subject to a storage challenge for three-dimensional imaging of a bulk region, such as breast. In this paper, a multi-scale mesh strategy based on computed tomography (CT) anatomical geometry is adopted to solve the storage challenge, where a fine mesh is used in forward calculation to ensure accuracy, and a coarse mesh in the inversion process to enable TSVD-based inversion of the whole-weighting matrix. We validate the proposed strategy using simulated data for a single lesion model from clinical positron emission tomography images of a breast cancer patient, and further, for a complex model that is constructed by setting dual lesions at different separations in the CT breast geometry.

Indirect and direct estimation of pharmacokinetic parameters in dynamic diffuse fluorescence tomography by adaptive extended Kalman filtering.

Pharmacokinetic parameter estimation with the support of dynamic diffuse fluorescence tomography (DFT) can provide helpful diagnostic information for tumor differentiation and monitoring. Adaptive extended Kalman filtering (AEKF) as a nonlinear filter method has the merits of high quantitativeness, noise robustness, and initialization independence. In this paper, indirect and direct AEKF schemes combining with a commonly used two-compartment model were studied to estimate the pharmacokinetic parameters based on our self-designed dynamic DFT system. To comprehensively compare the performances of both schemes, the selection of optimal noise covariance matrices affecting estimation results was first studied, then a series of numerical simulations with the metabolic time ranged from 4.16 min to 38 min was carried out and quantitatively evaluated. The comparison results show that the direct AEKF outperforms the indirect EKF in estimation accuracy at different metabolic velocity and demonstrates stronger stability at the large metabolic velocity. Furtherly, the in vivo experiment was conducted to achieve the indocyanine green pharmacokinetic-rate images in the mouse liver. The experimental results confirmed the capability of both schemes to estimate the pharmacokinetic-rate images and were in agreement with the theory predictions and the numerical simulation results.

All-optical ultrasonic detector based on differential interference.

We report on an all-optical ultrasonic detecting method based on differential interference. A linearly polarized probe beam is split into two closely separated ones with orthogonal polarization. After interacting with propagating ultrasonic waves in a coupling media, the split beams are recombined into one beam, with its polarization being changed into an elliptical one by the elastic-optical effect. The recombined beam is filtered by an analyzer and detected by a photodetector. The bandwidth and noise-equivalent pressure (NEP) of the acoustic detector are determined to be 107.4 MHz and 2.18 kPa, respectively. We also demonstrate its feasibility for photoacoustic microscopy (PAM) using agar-embedded phantoms.

Animal Detection and Classification from Camera Trap Images Using Different Mainstream Object Detection Architectures.

Camera traps are widely used in wildlife surveys and biodiversity monitoring. Depending on its triggering mechanism, a large number of images or videos are sometimes accumulated. Some literature has proposed the application of deep learning techniques to automatically identify wildlife in camera trap imagery, which can significantly reduce manual work and speed up analysis processes. However, there are few studies validating and comparing the applicability of different models for object detection in real field monitoring scenarios. In this study, we firstly constructed a wildlife image dataset of the Northeast Tiger and Leopard National Park (NTLNP dataset). Furthermore, we evaluated the recognition performance of three currently mainstream object detection architectures and compared the performance of training models on day and night data separately versus together. In this experiment, we selected YOLOv5 series models (anchor-based one-stage), Cascade R-CNN under feature extractor HRNet32 (anchor-based two-stage), and FCOS under feature extractors ResNet50 and ResNet101 (anchor-free one-stage). The experimental results showed that performance of the object detection models of the day-night joint training is satisfying. Specifically, the average result of our models was 0.98 mAP (mean average precision) in the animal image detection and 88% accuracy in the animal video classification. One-stage YOLOv5m achieved the best recognition accuracy. With the help of AI technology, ecologists can extract information from masses of imagery potentially quickly and efficiently, saving much time.

Extreme cold weather and circulatory diseases of older adults: A time-stratified case-crossover study in jinan, China.

OBJECTIVES: We aimed to investigate the acute effect of extreme cold weather on circulatory disease mortality of older adults in Jinan, with individual and regional-scale characteristics as subgroup analyses to further identify vulnerable populations. METHODS: This study contained the death data of Jinan from 2011 to 2020 (Nov-Mar). A time-stratified case-crossover method was used to estimate the effects of extreme cold weather and lags 0-8 days, controlling for holiday and relative humidity. To evaluate the impact of different durations and thresholds of extreme cold weather, we considered 4 cold day and 12 cold wave definitions RESULTS: Our results showed an increase in circulatory disease deaths under several definitions. The number of older adults died of circulatory diseases totaled 92,119 during the study period. In the definitions of cold day, the maximum significant effect ranging from 1.08 (95% CI: 1.03,1.14) to 1.13 (95% CI: 1.04,1.24) and appeared on Lag5 or Lag6. In the definitions of cold wave, the maximum significant effect ranging from 1.07 (95% CI: 1.02, 1.12) to 1.14 (95% CI: 1.03, 1.25). The cold effect is mainly attributable to cold day rather than an added effect related to the duration. Our research confirmed that extreme cold weather had a stronger impact on women [maximum effects with an OR of 1.21 (95% CI: 1.08, 1.36) in P1, 1.19 (95% CI: 1.05, 1.36) in M12)], and the effect gradient increased with age. CONCLUSIONS: Our findings support the evidence on the impact of extreme cold weather on circulatory disease mortality and provide a basis for policymakers to select target groups to develop policies and reduce the public health burden.