Sources and control of impurity during one-pot enzymatic production of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) has a promising market due to its capacity to regulate human hormone levels as well as preventing and treating various diseases. We have established a chemical esterification coupled biocatalytic-based scheme by lipase-catalyzed 4-androstene-3,17-dione (4-AD) hydrolysis to obtain the intermediate product 5-androstene-3,17-dione (5-AD), which was then asymmetrically reduced by a ketoreductase from Sphingomonas wittichii (SwiKR). Co-enzyme required for KR is regenerated by a glucose dehydrogenase (GDH) from Bacillus subtilis. This scheme is more environmentally friendly and more efficient than the current DHEA synthesis pathway. However, a significant amount of 4-AD as by-product was detected during the catalytic process. Focused on the control of by-products, we investigated the source of 4-AD and identified that it is mainly derived from the isomerization activity of SwiKR and GDH. Increasing the proportion of glucose in the catalytic system as well as optimizing the catalytic conditions drastically reduced 4-AD from 24.7 to 6.5% of total substrate amount, and the final yield of DHEA achieved 40.1 g/L. Furthermore, this is the first time that both SwiKR and GDH have been proved to be promiscuous enzymes with dehydrogenase and ketosteroid isomerase (KSI) activities, expanding knowledge of the substrate diversity of the short-chain dehydrogenase family enzymes. KEY POINTS: • A strategy of coupling lipase, ketoreductase, and glucose dehydrogenase in producing DHEA from 4-AD • Both SwiKR and GDH are identified with ketosteroid isomerase activity. • Development of catalytic strategy to control by-product and achieve highly selective DHEA production.

Pushing Pressure Detection Sensitivity to New Limits by Modulus-Tunable Mechanism.

Only microstructures are used to improve the sensitivity of iontronic pressure sensors. By modulating the compressive modulus, a breakthrough in the sensitivity of the iontronic pressure sensor is achieved. Furthermore, it allows for programmatic tailoring of sensor performance according to the requirements of different applications. Such a new strategy pushes the sensitivity up to a record-high of 25 548.24 kPa-1 and expands the linear pressure range from 15 to 127 kPa. Additionally, the sensor demonstrates excellent mechanical stability over 10 000 compression-release cycles. Based on this, a well-controlled robotic hand that precisely tracks the pressure behavior inside a balloon to autonomously regulate the gripping angle is developed. This paves the way for the application of iontronic pressure sensors in precise sensing scenarios.

Inflammatory factors and the risk of urolithiasis: a bidirectional Mendelian randomization study.

Background: Urolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive. Method: Mendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis. Results: Our study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848-0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-ß) (OR = 1.150, 95% CI = 1.009-1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1ß) (OR = 0.863, 95% CI = 0.779-0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (ß = 0.145, 95% CI = 0.013-0.276) and cutaneous T cell-attracting chemokine (CTACK) (ß = 0.145, 95% CI = 0.013-0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (ß = 0.142, 95% CI = 0.057-0.226), interleukin-7 (IL-7) (ß = 0.108, 95% CI = 0.024-0.192), interleukin-8 (IL-8) (ß = 0.127, 95% CI = 0.044-0.210), growth regulated oncogene alpha (GRO-α) (ß = 0.086, 95% CI = 0.004-0.169), monokine induced by interferon-gamma (MIG) (ß = 0.099, 95% CI = 0.008-0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (ß = 0.126, 95% CI = 0.044-0.208) levels. Conclusion: These discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-ß and MIP-1ß influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.

Preoperative prediction of microvascular invasion: new insights into personalized therapy for early-stage hepatocellular carcinoma.

Owing to advances in diagnosis and treatment methods over past decades, a growing number of early-stage hepatocellular carcinoma (HCC) diagnoses has enabled a greater of proportion of patients to receive curative treatment. However, a high risk of early recurrence and poor prognosis remain major challenges in HCC therapy. Microvascular invasion (MVI) has been demonstrated to be an essential independent predictor of early recurrence after curative therapy. Currently, biopsy is not generally recommended before treatment to evaluate MVI in HCC according clinical guidelines due to sampling error and the high risk of tumor cell seeding following biopsy. Therefore, the postoperative histopathological examination is recognized as the gold standard of MVI diagnosis, but this lagging indicator greatly impedes clinicians in selecting the optimal effective treatment for prognosis. As imaging can now noninvasively and completely assess the whole tumor and host situation, it is playing an increasingly important role in the preoperative assessment of MVI. Therefore, imaging criteria for MVI diagnosis would be highly desirable for optimizing individualized therapeutic decision-making and achieving a better prognosis. In this review, we summarize the emerging image characteristics of different imaging modalities for predicting MVI. We also discuss whether advances in imaging technique have generated evidence that could be practice-changing and whether advanced imaging techniques will revolutionize therapeutic decision-making of early-stage HCC.

Ionizable STING-Activating Nanoadjuvants Enhance Tumor Immunogenicity and Potentiate Immunotherapy Efficacy in Solid Tumors.

Therapeutic strategies that induce inflammatory responses in immunologically "cold" tumors have the potential to improve immunotherapeutic outcomes. Pharmacologically activating the STING pathway induces innate immunity, subsequently enhancing tumor immunogenicity. Here, we developed a nanoadjuvant with tumor-restricted pharmacology that rapidly activated STING and reshaped the tumor microenvironment (TME). The non-nucleotide STING agonist MSA-2 was chemically engineered with a piperazine motif linked by a saturated hydrocarbon chain of varying lengths to produce ionizable prodrugs that were further developed into nanoadjuvants. Compared with state-of-the-art liposomes, the nanoadjuvant displayed prolonged retention in the circulation and improved intratumoral delivery. In the acidic TME, the nanoadjuvant underwent polyethylene glycol deshielding, enabling efficient extravasation and penetration into tumors. Concomitantly, the STING prodrug escaped from the endo/lysosome compartment to partition into the cytosol for spontaneous esterase-catalyzed drug activation. In mouse models of syngeneic and chemically induced colorectal cancers, nanoparticle treatment provoked robust STING-mediated antitumor immunity, shifting the tumor immune landscape from immunosuppressed to tumoricidal. Additionally, the nanoadjuvant demonstrated antitumor efficacy in triple-negative breast cancer, which was further enhanced by the addition of immune checkpoint inhibitors. Collectively, this study demonstrates the safety and immune stimulating effects of a STING-activating nanoadjuvant, supporting the clinical evaluation of this STING immunotherapeutic alone and in combination with other immunotherapies.

The nicotine demethylase CYP82E4 is essential for the formation of red dapples on flue-cured leaves of cherry-red tobacco.

Common flue-cured tobacco (Nicotiana tabacum L.) primarily accumulates nicotine, and its flue-cured leaves exhibit a lemon appearance. In contrast, a spontaneous cherry-red variant (CR60) primarily accumulates nornicotine, accompanied by distinctive red dapples on the cured leaves. In this study, suppression of conversion of nicotine to nornicotine by genome editing resulted in decreased nornicotine and N-acyl nornicotines (NacNNs), and the subsequent disappearance of red dapples in CR60. Conversely, overexpression of CYP82E4 increased nornicotine and NacNNs accumulation, inducing a red dapple phenotype in common tobacco. Notably, nicotine conversion triggered significant alterations in leaf total sugars, alkaloids, and nitrogens. Metabolome analyses using 1352 identified compounds indicated nicotine conversion dramatically affected the entire metabolic network and induced unique metabolic responses across diverse genetic backgrounds. Further WGCNA analysis revealed that nicotine conversion caused substantial contents variation of alkaloids, flavonoids and amino acids and derivatives in cured leaves. Overall, this research provides valuable insights into the mechanisms underlying red dapple formation in cherry-red tobacco, elucidating profound influence of nicotine conversion on entire metabolic network.

Idiopathic giant adrenal calcification: a rare case report.

Background: We describe a rare case of giant adrenal calcification as the main cause of sudden onset epigastric pain in a 57-year-old female patient. Case description: Computed tomography (CT) of the whole abdomen in this patient showed calcified foci measuring approximately 7.8 × 5.4 × 7.1 cm in the hepatorenal recess, and no enhancement effect was seen. Secondary causes of adrenal calcification in this patient were ruled out, and a rare diagnosis of a primary giant adrenal calcification was made. Subsequently, the right adrenal gland and calcified mass were completely resected. The calcification did not recur during 6 months of follow up. Conclusions: Although other cases of adrenal calcification of unknown origin have been reported, cases of giant idiopathic adrenal calcification are rare. In this case, huge calcification of the right adrenal gland caused abdominal pain, which disappeared after the mass was excised. The etiology, pathogenesis, clinical symptoms, and prognosis of idiopathic adrenal calcification are still unclear. Additional case reports are needed to gain a better understanding of the diagnosis and treatment of this condition.

Superconductivity in pressurized trilayer La4Ni3O10-δ single crystals.

The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.

Identification and impact of failure of pelvic compensation in patients with adult spinal deformity.

BACKGROUND CONTEXT: Previous research has identified a specific subtype known as failure of pelvic compensation (FPC) in patients with adult spinal deformity (ASD). However, the criteria for assessing FPC remain inconsistent, and its impacts on spinal sagittal alignment and health-related quality-of-life (HRQoL) scores remain unclear. PURPOSE: To propose a novel criterion for identifying FPC based on variations in spinopelvic alignment during the transition from the supine to upright position and to evaluate the effects of FPC on patients' spinal sagittal alignment and HRQoL scores. STUDY DESIGN/SETTING: Retrospective cross-sectional study. PATIENT SAMPLE: Patients with ASD from a monocenter database. OUTCOME MEASURES: Radiographic measures, including thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt, pelvic incidence (PI), and sagittal vertical axis (SVA), were measured on lateral whole-spine radiographs. LL and SS were also measured on reconstructed lumbar computed tomography images in the sagittal view taken in the supine position. The relative functional cross-sectional area (rFCSA) of paraspinal muscles was evaluated via lumbar magnetic resonance imaging. HRQoL measures, encompassing visual analog scale for back pain (VAS-BP), Oswestry Disability Index (ODI), and Scoliosis Research Society-22R (SRS-22R), were collected. METHODS: A total of 154 patients were enrolled. Based on the calculated minimum detectable change of SS, FPC was defined as the change in SS of less than 3.4° between supine and upright positions. Patients were divided into 3 groups: sagittal balance with pelvic compensation (SI-PC), sagittal imbalance with pelvic compensation (SI-PC), and sagittal imbalance with failure of pelvic compensation (SI-FPC). Radiographic parameters and HRQoL scores were compared among the groups. RESULTS: Thirty-six patients were categorized into the SB-PC group, 87 into the SI-PC group, and 31 into the SI-FPC group. Patients with low PI and small paraspinal muscles rFCSA were more prone to experiencing FPC accompanied by severe sagittal imbalance. The SI-FPC group exhibited less TK and a larger SS than the SI-PC group exhibited and had a similar SVA as that of the SI-PC group. Additionally, they displayed worse VAS-BP, ODI, SRS-function, and SRS-22 total scores than the SB-PC group displayed. CONCLUSIONS: In patients with ASD, an inherently low pelvic compensatory reserve and a high fatty infiltration in paraspinal muscles are pivotal factors contributing to FPC. Compared with SI-PC patients, SI-FPC patients demonstrate a thoracic-dominant compensatory pattern for sagittal malalignment. In addition, these patients experienced more severe pain and functional decline than the SB-PC patients experienced.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Spinal column radiological factors associated with increased spinal cord intramedullary signal intensity - A study evaluating aging spinal cord's relation to spinal disc degeneration.

PURPOSE: Increased intramedullary signal intensity (IISI) on T2 weighted MRI scan (T2WI) can be a radiological feature of spinal cord degeneration. However, the association of IISI to degeneration of the spinal column that protects the spinal cord remains unclear. The purpose of this study was to determine the prevalence of IISI and analyze the independent relationship between IISI and cervical degenerative parameters on X-ray and magnetic resonance imaging (MRI). METHODS: A retrospective review of MRI, X-ray, and radiology data (n = 144) adult patients with both cervical MRI and X-ray scans was conducted. A total of 39 (27 %) patients with IISI was identified. The remaining 105 patients without IISI made up the control group. RESULTS: IISI was most frequent in C6-C7 cervical levels. The likelihood of having IISI was 1.947 (Exp(B) 1.947, 95 %CI [1.004-3.776]) times higher in segmental levels with facet joint degeneration. There was an increased likelihood of IISI within the spinal cord with increasing age (Exp(B) 1.034, 95 %CI [1.008-1.060]), maximum spinal cord compression (MSCC) (Exp(B) 1.038, 95 %CI [1.003-1.075]), rotational angle (Exp(B) 1.082, 95 %CI [1.020-1.148]) and posterior disc herniation width (Exp(B) 1.333, 95 %CI [1.017-1.747]) and decreasing Torg-Pavlov ratio (Exp(B) 0.010, 95 %CI [0.001-0.068]). CONCLUSION: IISI was independently associated with increased age, facet joint degeneration, MSCC, rotational angle, posterior herniation width and decreasing Torg-Pavlov angle. Radiologicaldegenerative changesassociated with IISI indicates a potential for identifying predictors of age related spinal cord morphological changes in DCM, which may allow for early intervention strategies in the future.

Trends in Undernutrition among Macao Children and Adolescents Aged 7~18 Years: An Analysis from Four Successive Macau Government Surveys from 2005 to 2020.

Background: We aimed to explore the epidemiological trends and characteristics of undernutrition among children and adolescents aged 7~18 years in Macao from 2005 to 2020 to provide insights into the improvement of nutritional status among the youth in Macao, China. Methods: Based on the data collected from the Citizen Physical Fitness surveillance sessions in Macao in 2005, 2010, 2015, and 2020, the prevalence of undernutrition among children and adolescents aged 7~18 years in Macao was calculated. Result: In 2020, the prevalence of undernutrition among children and adolescents aged 7~18 years in Macao was 12.11%. Among them, the rates of stunting, moderate or severe wasting, and mild wasting were 0.63%, 5.25%, and 6.23%, respectively. The prevalence of undernutrition among boys (13.81%) was higher than that among girls (10.06%). Mild wasting was the main form of undernutrition among students. From 2005 to 2020, the prevalence of malnutrition showed a decreasing trend (P<0.05), but there was a rebound in 2020 from 2015, mainly because it may be caused by the COVID-19 pandemic in 2020. The prevalence of undernutrition among children and adolescents in Macao was lower than that in Mainland China (P<0.01). Conclusion: The detection rates of undernutrition showed a decreasing trend from 2005 to 2020. In the post-pandemic era, Macao should undertake more effective measures in areas such as promoting balanced nutritional intake, increasing physical activity levels, enhancing school physical education, and incorporating mental health education. These efforts are essential for further reducing the prevalence of undernutrition among children and adolescents.

Monolithic integrated optoelectronic chip for vector force detection.

Sensors with a small footprint and real-time detection capabilities are crucial in robotic surgery and smart wearable equipment. Reducing device footprint while maintaining its high performance is a major challenge and a significant limitation to their development. Here, we proposed a monolithic integrated micro-scale sensor, which can be used for vector force detection. This sensor combines an optical source, four photodetectors, and a hemispherical silicone elastomer component on the same sapphire-based AlGaInP wafer. The chip-scale optical coupling is achieved by employing the laser lift-off techniques and the flip-chip bonding to a processed sapphire substrate. This hemispherical structure device can detect normal and shear forces as low as 1 mN within a measurement range of 0-220 mN for normal force and 0-15 mN for shear force. After packaging, the sensor is capable of detecting forces over a broader range, with measurement capabilities extending up to 10 N for normal forces and 0.2 N for shear forces. It has an accuracy of detecting a minimum normal force of 25 mN and a minimum shear force of 20 mN. Furthermore, this sensor has been validated to have a compact footprint of approximately 1.5 mm2, while maintaining high real-time response. We also demonstrate its promising potential by combining this sensor with fine surface texture perception in the fields of compact medical robot interaction and wearable devices.

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

The Role of Pelvic Compensation in Sagittal Balance and Imbalance: The Impact of Pelvic Compensation on Spinal Alignment and Clinical Outcomes Following Adult Spinal Deformity Surgery.

BACKGROUND AND OBJECTIVES: The Scoliosis Research Society (SRS)-Schwab system does not include a pelvic compensation (PC) subtype, potentially contributing to gaps in clinical characteristics and treatment strategy for deformity correction. It also remains uncertain as to whether PC has differing roles in sagittal balance (SB) or imbalance (SI) status. To compare radiological parameters and SRS-22r domains between patients with failed pelvic compensation (FPC) and successful pelvic compensation (SPC) based on preoperative SB and SI. METHODS: A total of 145 adult spinal deformity patients who received deformity correction were analyzed. Radiographic and clinical outcomes were collected for statistical analysis. Patients were classified into 4 groups based on the median value of PT/PI ratio (PTr) and the cutoff value of SB. Patients with low PTr and high PTr were defined as FPC and SPC, respectively. Radiographic and clinical characteristics of different groups were compared. RESULTS: Patients with SPC exhibited significantly greater improvements in lumbar lordosis, pelvic tilt, PTr, and T1 pelvic angle as compared to patients with FPC, irrespective of SB or SI. No apparent differences in any of SRS-22r domains were observed at follow-up when comparing the SB-FPC and SB-SPC patients. However, patients with SI-SPC exhibited significantly better function, self-image, satisfaction, and subtotal domains at follow-up relative to those with SI-FPC. When SI-FPC and SI-SPC patients were subdivided further based on the degree of PI-LL by adjusting for age, the postoperative function and self-image domains were significantly better in the group with overcorrection of PI-LL than undercorrection of PI-LL in SI-FPC patients. However, no differences in these SRS-22r scores were observed when comparing the subgroups in SI-SPC patients. CONCLUSION: Flexible pelvic rotation is associated with benefits to the correction of sagittal parameters, irrespective of preoperative SB or SI status. However, PC is only significantly associated with clinical outcomes under SI. Patients with SI-FPC exhibit poorer postoperative clinical outcomes, which should be recommended to minimize PI-LL.

3.05 kW, 13.7 GHz linewidth fiber amplifier based on PRBS phase modulation for SBS suppression.

In this paper, we establish a multi-stage fiber amplifier with pseudo-random binary sequence (PRBS) phase modulation. The stimulated Brillouin gain spectra of the main amplifier with both the unmodulated and pseudo-random binary sequence phase modulated configuration are measured (with corresponding output power), and the stimulated Brillouin scattering (SBS) threshold is investigated experimentally and theoretically. The pseudo-random binary sequence phase modulation parameters are optimized by theoretical simulation. With a two-stage preamplifier chain and a counter-pumping main amplifier stage, a maximum 3.05 kW output power with a slope efficiency of 85.9% is obtained experimentally. The central wavelength of the fiber amplifier is 1050 nm, associated with a full-width at half-maximum linewidth of 13.7 GHz. The stimulated Brillouin scattering reflectivity is below 0.01% at 3.05 kW at 13.7 GHz, which indicates that stimulated Brillouin scattering can be suppressed efficiently at this power and linewidth level.

Nanoparticles targeting the adenosine pathway for cancer immunotherapy.

Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.

A Retrospective Investigation of a Case of Dual Infection by Avian-Origin Influenza A (H10N5) and Seasonal Influenza A (H3N2) Viruses - Anhui Province, China, December 2023-January 2024.

What is known about this topic?: H10 avian influenza viruses circulate in wild birds and can reassort with other subtypes. H10N8 and H10N3 have previously caused sporadic human infections in China. What is added by this report?: This report documents the first human case of co-infection with avian-origin H10N5 and seasonal H3N2 influenza viruses. Epidemiological investigations identified H10N5 in environmental samples linked to the patient, but no transmission to close contacts occurred. What are the implications for public health practice?: Enhanced surveillance of avian influenza in live poultry markets and poultry populations is crucial for thoroughly characterizing the epidemiology, transmission, and pathogenesis of H10N5 viruses. Strengthening assessments of outbreak control measures is essential to guide effective management.

Developmental origins shape the paediatric cancer genome.

In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations.