FNeXter: A Multi-Scale Feature Fusion Network Based on ConvNeXt and Transformer for Retinal OCT Fluid Segmentation.

The accurate segmentation and quantification of retinal fluid in Optical Coherence Tomography (OCT) images are crucial for the diagnosis and treatment of ophthalmic diseases such as age-related macular degeneration. However, the accurate segmentation of retinal fluid is challenging due to significant variations in the size, position, and shape of fluid, as well as their complex, curved boundaries. To address these challenges, we propose a novel multi-scale feature fusion attention network (FNeXter), based on ConvNeXt and Transformer, for OCT fluid segmentation. In FNeXter, we introduce a novel global multi-scale hybrid encoder module that integrates ConvNeXt, Transformer, and region-aware spatial attention. This module can capture long-range dependencies and non-local similarities while also focusing on local features. Moreover, this module possesses the spatial region-aware capabilities, enabling it to adaptively focus on the lesions regions. Additionally, we propose a novel self-adaptive multi-scale feature fusion attention module to enhance the skip connections between the encoder and the decoder. The inclusion of this module elevates the model's capacity to learn global features and multi-scale contextual information effectively. Finally, we conduct comprehensive experiments to evaluate the performance of the proposed FNeXter. Experimental results demonstrate that our proposed approach outperforms other state-of-the-art methods in the task of fluid segmentation.

DAB2IP stabilizes p27Kip1 via suppressing PI3K/AKT signaling in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most lethal of the urologic malignancies. We previously discovered that DAB2IP, a novel Ras GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. In this study, we determined the biological functions of DAB2IP in clear cell RCC (ccRCC) and its potential mechanisms of action. Correlations between DAB2IP expression level and ccRCC tumor size and patient survival were analyzed, and the results showed that ccRCC patients with high DAB2IP mRNA level exhibited smaller tumor size and better survival than the patients with low DAB2IP. Compared to control, DAB2IP knockdown significantly increased cell proliferation, promoted cell cycle progression in G1/S phase, and decreased p27 expression. Mechanism studies demonstrated that loss of DAB2IP promoted p27 protein phosphorylation, cytosolic sequestration, and subsequently ubiquitination-mediated degradation in ccRCC cells. Further studies confirmed that the proline-rich domain in C terminal (CPR) of DAB2IP suppressed AKT phosphorylation and p27 phosphorylation on S10. Hence, DAB2IP is essential for p27 protein stabilization in ccRCC, which is at less partly mediated by PI3K/AKT signaling pathway.

Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study.

BACKGROUND: Despite the substantial burden caused by childhood cancer globally, childhood cancer incidence obtained in a nationwide childhood cancer registry and the accessibility of relevant health services are still unknown in China. We comprehensively assessed the most up-to-date cancer incidence in Chinese children and adolescents, nationally, regionally, and in specific population subgroups, and also examined the association between cancer incidence and socioeconomic inequality in access to health services. METHODS: In this national cross-sectional study, we used data from the National Center for Pediatric Cancer Surveillance, the nationwide Hospital Quality Monitoring System, and public databases to cover 31 provinces, autonomous regions, and municipalities in mainland China. We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China through stratified proportional estimation. We classified regions by socioeconomic status using the human development index (HDI). Incidence rates of 12 main groups, 47 subgroups, and 81 subtypes of cancer were reported and compared by sex, age, and socioeconomic status, according to the third edition of the International Classification of Childhood Cancer. We also quantified the geographical and population density of paediatric oncologists, pathology workforce, diagnoses and treatment institutions of paediatric cancer, and paediatric beds. We used the Gini coefficient to assess equality in access to these four health service indicators. We also calculated the proportions of cross-regional patients among new cases in our surveillance system. FINDINGS: We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China from Jan 1, 2018, to Dec 31, 2020. An estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, with world standard age-standardised incidence rates of 122·86 (95% CI 121·70-124·02) per million for children and 137·64 (136·08-139·20) per million for adolescents. Boys had a higher incidence rate of childhood cancer (133·18 for boys vs 111·21 for girls per million) but a lower incidence of adolescent cancer (133·92 for boys vs 141·79 for girls per million) than girls. Leukaemias (42·33 per million) were the most common cancer group in children, whereas malignant epithelial tumours and melanomas (30·39 per million) surpassed leukaemias (30·08 per million) in adolescents as the cancer with the highest incidence. The overall incidence rates ranged from 101·60 (100·67-102·51) per million in very low HDI regions to 138·21 (137·14-139·29) per million in high HDI regions, indicating a significant positive association between the incidence of childhood and adolescent cancer and regional socioeconomic status (p<0·0001). The incidence in girls showed larger variation (48·45% from the lowest to the highest) than boys (36·71% from lowest to highest) in different socioeconomic regions. The population and geographical densities of most health services also showed a significant positive correlation with HDI levels. In particular, the geographical density distribution (Gini coefficients of 0·32-0·47) had higher inequalities than population density distribution (Gini coefficients of 0·05-0·19). The overall proportion of cross-regional patients of childhood and adolescent cancer was 22·16%, and the highest proportion occurred in retinoblastoma (56·54%) and in low HDI regions (35·14%). INTERPRETATION: Our study showed that the burden of cancer in children and adolescents in China is much higher than previously nationally reported from 2000 to 2015. The distribution of the accessibility of health services, as a social determinant of health, might have a notable role in the socioeconomic inequalities in cancer incidence among Chinese children and adolescents. With regards to achieving the Sustainable Development Goals, policy approaches should prioritise increasing the accessibility of health services for early diagnosis to improve outcomes and subsequently reduce disease burdens, as well as narrowing the socioeconomic inequalities of childhood and adolescent cancer. FUNDING: National Major Science and Technology Projects of China, National Natural Science Foundation of China, Chinese Academy of Engineering Consulting Research Project, Wu Jieping Medical Foundation, Beijing Municipal Administration of Hospitals Incubating Program.

Folate intake and non-alcoholic fatty liver disease in US adults.

BACKGROUND AND OBJECTIVES: The relationship between dietary folate intake and non-alcoholic fatty liver disease (NAFLD) is controversial. This study aimed to investigate the relationship between dietary folate equivalent (DFE) intake and NAFLD in U.S. adults. METHODS AND STUDY DESIGN: Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used. NAFLD was defined as a US fatty liver index (FLI) value ≥30. DFE intake was assessed by two 24-hour dietary recall interviews. Multivariable logistic regression models and restricted cubic spline models were used to investigate the association between DFE intake and NAFLD risk. RESULTS: A total of 6,603 adult participants were included in this study. After adjusting for multiple confounding factors, the odds ratios and 95% confidence intervals of NAFLD for the highest quartile versus lowest quartile of DFE intake was 0.77(0.59-0.99). In stratified analyses by sex, age, and body mass index (BMI), there were statistically significant negative associations between DFE intake and NAFLD risk in women and participants with BMI ≥25. Dose-response analysis indicated a negative linear correlation between DFE intake and NAFLD risk. CONCLUSIONS: Dietary folate equivalent intake is negatively associated with NAFLD risk in the general U.S. adult population.

A modular and self-adjuvanted multivalent vaccine platform based on porcine circovirus virus-like nanoparticles.

BACKGROUND: Virus-like particles (VLPs) are supramolecular structures composed of multiple protein subunits and resemble natural virus particles in structure and size, making them highly immunogenic materials for the development of next-generation subunit vaccines. The orderly and repetitive display of antigenic epitopes on particle surface allows efficient recognition and cross-link by B cell receptors (BCRs), thereby inducing higher levels of neutralizing antibodies and cellular immune responses than regular subunit vaccines. Here, we present a novel multiple antigen delivery system using SpyCatcher/Spytag strategy and self-assembled VLPs formed by porcine circovirus type 2 (PCV2) Cap, a widely used swine vaccine in solo. RESULTS: Cap-SC, recombinant Cap with a truncated SpyCatcher polypeptide at its C-terminal, self-assembled into 26-nm VLPs. Based on isopeptide bonds formed between SpyCatcher and SpyTag, classical swine fever virus (CSFV) E2, the antigen of interest, was linked to SpyTag and readily surface-displayed on SpyCatcher decorated Cap-SC via in vitro covalent conjugation. E2-conjugated Cap VLPs (Cap-E2 NPs) could be preferentially captured by antigen presenting cells (APCs) and effectively stimulate APC maturation and cytokine production. In vivo studies confirmed that Cap-E2 NPs elicited an enhanced E2 specific IgG response, which was significantly higher than soluble E2, or the admixture of Cap VLPs and E2. Moreover, E2 displayed on the surface did not mask the immunodominant epitopes of Cap-SC VLPs, and Cap-E2 NPs induced Cap-specific antibody levels and neutralizing antibody levels comparable to native Cap VLPs. CONCLUSION: These results demonstrate that this modularly assembled Cap-E2 NPs retains the immune potential of Cap VLP backbone, while the surface-displayed antigen significantly elevated E2-induced immune potency. This immune strategy provides distinctly improved efficacy than conventional vaccine combination. It can be further applied to the development of dual or multiple nanoparticle vaccines to prevent co-infection of PCV2 and other swine pathogens.

Characteristics of thin InAlAs digital alloy avalanche photodiodes.

InP-based avalanche photodiodes (APDs) are widely used in short-wave infrared (SWIR) communications. In this work, a thin (200 nm nominal) InAlAs digital alloy layer consisting of two monolayer (ML) InAs and two ML AlAs was grown on InP substrate and investigated in detail. APDs with p-i-n and n-i-p structures were fabricated and characterized. The current-voltage, capacitance-voltage characteristics, and excess noise were measured at room temperature with different laser wavelengths, and the measured effective k value (ratio of impact ionization coefficients) is about 0.15 with the multiplication gain up to 12. The randomly-generated path length (RPL) model was carried out to analyze the dead space effect. Our thin digital alloy successfully reduced excess noise compared with conventional In0.52Al0.48As random alloy without introducing new elements and shows the potential for high-speed, low noise APD applications.

Defect characterization of AlInAsSb digital alloy avalanche photodetectors with low frequency noise spectroscopy.

An avalanche photodetector (APD) based on the AlxIn1-xAsySb1-y digital alloy materials system has recently attracted extensive attention due to its extremely low excess noise. Device defects are a critical factor limiting the performance of APDs. In this work, we use low frequency noise spectroscopy (LFNS) to characterize the property of the defects in AlxIn1-xAsySb1-y APDs grown by molecular beam epitaxy (MBE) using the digital alloy technique. Based on low frequency noise spectroscopy results carried out before and after device oxidation, two surface defects and one bulk defect have been identified, which could provide useful information for the future optimization the material growth and device fabrication processes.

Low frequency noise-dark current correlations in HgCdTe infrared photodetectors.

In this paper, low frequency noise and dark current correlation is investigated as a function of reverse bias and temperature for short-wave infrared (SWIR), mid-wave infrared (MWIR), and long-wave infrared (LWIR) HgCdTe homo-junction photodetectors. Modelling of dark current-voltage characteristics shows that the detectors have ohmic-behavior under small reverse bias, thus enabling further analysis of 1/f noise-current dependences with the empirical square-law relation (SI ∼ I2) at different temperature regions. It is found that for the SWIR and MWIR devices, the total 1/f noise spectral density at arbitrary temperatures can be modelled by the sum of shunt and generation-recombination noise as SI(T,f)=[αSHISH2(T)+αG-RIG-R2(T)]/f, with no contribution from the diffusion component observed. On the other hand, for the LWIR device the diffusion component induced 1/f noise that cannot be overlooked in high temperature regions, and a 1/f noise-current correlation of SI(T,f)={αs[IDIFF2(T)+IG-R2(T)]+αSHISH2(T)}/f is proposed, with a shared noise coefficient of αs ≅ 1 × 10-9 which is close to that calculated for shunt noise. The 1/f noise-current correlation established in this work can provide a powerful tool to study the low frequency noise characteristics in HgCdTe-based photodetectors and to help optimizing the "true" detectivity of devices operating at low frequency regime.

High-speed mid-wave infrared interband cascade photodetector at room temperature.

High-speed mid-wave infrared (MWIR) photodetectors have important applications in the emerging areas such high-precision frequency comb spectroscopy and light detection and ranging (LIDAR). In this work, we report a high-speed room-temperature mid-wave infrared interband cascade photodetector based on a type-II InAs/GaSb superlattice. The devices show an optical cut-off wavelength around 5 µm and a 3-dB bandwidth up to 7.04 GHz. The relatively low dark current density around 9.39 × 10-2 A/cm2 under -0.1 V is also demonstrated at 300 K. These results validate the advantages of ICIPs to achieve both high-frequency operation and low noise at room temperature. Limitations on the high-speed performance of the detector are also discussed based on the S-parameter analysis and other RF performance measurement.

Enhancing Sensor Network Security with Improved Internal Hardware Design.

With the rapid development of the Internet-of-Things (IoT), sensors are being widely applied in industry and human life. Sensor networks based on IoT have strong Information transmission and processing capabilities. The security of sensor networks is progressively crucial. Cryptographic algorithms are widely used in sensor networks to guarantee security. Hardware implementations are preferred, since software implementations offer lower throughout and require more computational resources. Cryptographic chips should be tested in a manufacturing process and in the field to ensure their quality. As a widely used design-for-testability (DFT) technique, scan design can enhance the testability of the chips by improving the controllability and observability of the internal flip-flops. However, it may become a backdoor to leaking sensitive information related to the cipher key, and thus, threaten the security of a cryptographic chip. In this paper, a secure scan test architecture was proposed to resist scan-based noninvasive attacks on cryptographic chips with boundary scan design. Firstly, the proposed DFT architecture provides the scan chain reset mechanism by gating a mode-switching detection signal into reset input of scan cells. The contents of scan chains will be erased when the working mode is switched between test mode and functional mode, and thus, it can deter mode-switching based noninvasive attacks. Secondly, loading the secret key into scan chains of cryptographic chips is prohibited in the test mode. As a result, the test-mode-only scan attack can also be thwarted. On the other hand, shift operation under functional mode is disabled to overcome scan attack in the functional mode. The proposed secure scheme ensures the security of cryptographic chips for sensor networks with extremely low area penalty.

Securing Cryptographic Chips against Scan-Based Attacks in Wireless Sensor Network Applications.

Wireless sensor networks (WSN) have deeply influenced the working and living styles of human beings. Information security and privacy for WSN is particularly crucial. Cryptographic algorithms are extensively exploited in WSN applications to ensure the security. They are usually implemented in specific chips to achieve high data throughout with less computational resources. Cryptographic hardware should be rigidly tested to guarantee the correctness of encryption operation. Scan design improves significantly the test quality of chips and thus is widely used in semiconductor industry. Nevertheless, scan design provides a backdoor for attackers to deduce the cipher key of a cryptographic core. To protect the security of the cryptographic system we first present a secure scan architecture, in which an automatic test control circuitry is inserted to isolate the cipher key in test mode and clear the sensitive information at mode switching. Then, the weaknesses of this architecture are analyzed and an enhanced scheme using concept of test authorization is proposed. If the correct authorization key is applied within the specific time, the normal test can be performed. Otherwise, only secure scan test can be performed. The enhanced scan scheme ensures the security of cryptographic chips while remaining the advantages of scan design.

Dynamic model and bandwidth characterization of InGaAs/GaAsSb type-II quantum wells PIN photodiodes.

In this work, we demonstrated a normal incident PIN InGaAs/GaAsSb type-II multiple quantum wells (MQW) photodiode on InP substrate for 2 µm wavelength high-speed operation. The photodiode has a responsivity of 0.35 A/W at room temperature at 2 µm, and a 3 dB bandwidth of 3.7 GHz. A carrier dynamic model is developed to study the bandwidth of the multiple quantum wells photodiode. Simulation results match the experimental data well, and analysis shows that hole transport limits the 3 dB bandwidth performance. By optimizing the MQW design, higher bandwidth performance (>10 GHz) can be achieved.

A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC).

BACKGROUND: This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients. METHODS: The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated. RESULTS: A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = - 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode. CONCLUSION: NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

Influence of endoscopic sinus surgery on the quality of life of patients with early nasopharyngeal carcinoma and the analysis of prognosis-related factors.

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ2 = 4.403, p = 0.036; χ2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.

Switchable generation of rectangular noise-like pulse and dissipative soliton resonance in a fiber laser.

We report on the switchable generation of a rectangular noise-like pulse (NLP) and a dissipative soliton resonance (DSR) in a fiber laser with highly nonlinear effect at very low pump power. The NLP centered at 1530.5 nm demonstrates a new characteristic that its profile evolves gradually from rectangular shape to Gaussian-like shape with the increasing pump power. By appropriately manipulating the polarization controller (PC), the laser switches emit a DSR pulse centered at 1551.3 nm. The duration of the DSR could broaden from 17.4 ns to the cavity round trip time with increasing the pump power, while keeping the pulse profile and the intensity unaltered. This type of fiber laser may not only facilitate further investigations of the characteristics of NLP and DSR but also serve as a multi-functional optical source for potential applications.

[Diagnosis and Treatment of the First Imported Case of Plasmodium knowlesi Infection in China].

Objective: To diagnose and treat the first imported active case of Plasmodium knowlesi infection in China. Methods: The clinical information of the patient was collected. Microscopy of blood smear was conducted after Giemsa staining. Genomic DNA was extracted from blood, and PCR was conducted to amplify rDNA. The PCR products were sequenced and analyzed with BLAST Results: The patient returned from a one-week tour in a tropical rain forest in Malaysia. The first disease attack occurred in Guangzhou on Oct. 16, 2014, with fever, shivering and sweating. The patient was initially diagnosed as malaria and hospitalized on Oct. 26, 2014. Microscopic observation revealed typical forms of P. knowlesi in blood smear. The red blood cells became enlarged, with big trophozoites appearing as a ring with dual cores and dark brown malaria pigment. The trophozoites were slightly bigger and thicker than P. falciparum. The schizont had 6-8 merozoites, with obvious brown malaria pigment. PCR resulted in a specific band of 1 099 bp. BLAST analysis showed that the sequence of the PCR product was 99% homologous to P. knowlesi (acession No. AM910985.1, L07560.1 and AY580317.1). The patient was diagnosed as P. knowlesi infection, and was then given an 8-day treatment with chloroquine and primaquine, together with dihydroartemisinin piperaquine phosphate tablet. The patient was discharged after recovery on Oct. 28, 2014. Conclusion: According to the clinical symptoms, epidemiological history and laboratory test, the patient has been confirmed as P. knowlesi infection. It may also be the first active case of knowlesi malaria reported in China.

Headspace thin-film microextraction coupled with surface-enhanced Raman scattering as a facile method for reproducible and specific detection of sulfur dioxide in wine.

By coupling thin-film microextraction (TFME) with surface-enhanced Raman scattering (SERS), a facile method was developed for the determination of sulfur dioxide (SO2), the most effective food additive in winemaking technology. The TFME substrate was made by free settling of sea urchin-like ZnO nanomaterials on a glass sheet. The headspace sampling (HS) procedure for SO2 was performed in a simple homemade device, and then the SO2 was determined using SERS after uniformly dropping or spraying a SERS-active substrate (gold nanoparticles, AuNPs) onto the surface of the TFME substrate. A reproducible and strong SERS response of the SO2 absorbed onto the ZnO substrate was obtained. After condition optimization, the SERS signal intensity at a shift of 600 cm(-1) and the SO2 concentration showed a good linearity in the range of 1-200 µg/mL, and the linear correlation coefficient was 0.992. The detection limit for SO2 was found to be 0.1 µg/mL. The HS-TFME-SERS method was applied for the determination of SO2 in wine, and the results obtained agreed very well with those obtained using the traditional distillation and titration method. Analysis of variance and Student t test show that there is no significant difference between the two methods, indicating that the newly developed method is fast, convenient, sensitive and has selective characteristics in the determination of SO2 in wine.

Electrospray ionization-tandem mass spectrometry method for differentiating chlorine substitution in disinfection byproduct formation.

An electrospray ionization-tandem mass spectrometry (ESI-tqMS) method was developed to identify the location of chlorine substitution during the chlorination of model organic compounds. The chlorine substitution in the aliphatic part and that in the benzene ring of an organic molecule can be differentiated by their corresponding ranges of optimum collision energies, 5-7 eV and over 15 eV, respectively, in the precursor ion scan of m/z 35. The method was applied to predict the structures of intermediates and reveal the transformation pathways during the chlorination of 4-amino-2-chlorobenzoic acid and phenylalanine as a function of reaction time and the chlorine-to-precursor ratio. In the case of phenylalanine, chlorine was found to replace one hydrogen atom attached to the aliphatic nitrogen; in the case of 4-amino-2-chlorobenzoic acid, chlorine was found to replace the hydrogen atoms attached to the aromatic rings.

Obesity impairs revascularization and bone healing in a mouse model of osteonecrosis.

Osteonecrosis of the femoral head (ONFH) is a devastating bone disease that is caused by a disruption of blood supply leading to necrotic cell death. Clinically, it was found that obesity has a high prevalence with ONFH. However, it remains unclear how obesity may directly affect tissue regeneration and bone healing in osteonecrosis (ON). The purpose of this study is to investigate the effects of obesity and weight loss (WL) on ON healing. In this study, we induced obesity and WL in an established surgery-induced ON mouse model via feeding a high-fat diet (HFD) and altering the diet respectively. All mice received a surgical induction of ON of distal femoral epiphysis at the age of 12 weeks. HFD was switched to normal diet (ND) after ON surgery to induce WL. Mouse body weight was recorded weekly. Mouse body composition was scanned by DEXA (Dual-energy X-ray absorptiometry) right after sacrifice at the age of 16 weeks. The distal femoral bone samples were fixed and embedded for histology such as H&E, immunohistochemistry, and TRAP staining. In this study, we found that HFD-induced obesity impaired revascularization and bone remodeling showing decreased vessel areas and reduced osteoblast and osteoclast numbers. WL could rescue obesity-induced bone healing defects. Our study is the first to test the direct effects of obesity and WL on ON bone healing. We believe our work may provide new concepts for osteonecrosis treatment in obese patients.

m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.