Recent advances in microbial synthesis of free heme.

Heme is an iron-containing porphyrin compound widely used in the fields of healthcare, food, and medicine. Compared to animal blood extraction, it is more advantageous to develop a microbial cell factory to produce heme. However, heme biosynthesis in microorganisms is tightly regulated, and its accumulation is highly cytotoxic. The current review describes the biosynthetic pathway of free heme, its fermentation production using different engineered bacteria constructed by metabolic engineering, and strategies for further improving heme synthesis. Heme synthetic pathway in Bacillus subtilis was modified utilizing genome-editing technology, resulting in significantly improved heme synthesis and secretion abilities. This technique avoided the use of multiple antibiotics and enhanced the genetic stability of strain. Hence, engineered B. subtilis could be an attractive cell factory for heme production. Further studies should be performed to enhance the expression of heme synthetic module and optimize the expression of heme exporter and fermentation processes, such as iron supply. KEY POINTS: • Strengthening the heme biosynthetic pathway can significantly increase heme production. • Heme exporter overexpression helps to promote heme secretion, thereby further promoting excessive heme synthesis. • Engineered B. subtilis is an attractive alternative for heme production.

DRAGON: Harnessing the power of DNA repair for accelerating genome evolution in Corynebacterium glutamicum.

Hypermutation is a robust phenotype characterized by high elevation of spontaneous mutation rates, which has been shown to facilitate rapid adaptation to the stressful environments by hitchhiking with favorable mutations. Accumulating evidence argues that deficient DNA repair can give rise to hypermutation events in bacteria. Here, we provided a comprehensive survey of DNA repair systems to identify promising targets ensuring high DNA fidelity in Corynebacterium glutamicum. Four effective DNA repair factors, including nucS, tag, xpb, and dinP, were found to be strongly associated with the occurrence of hypermutable phenotypes, and these targets were then engineered to establish a CRISPRi-based all-in-one plasmid system for genome mutagenesis. On the basis of these findings, we presented a novel evolutionary engineering method named "DNA repair-assisted genome evolution (DRAGON)". As a proof-of-concept, DRAGON strategy was successfully applied to facilitate rapid acquisition of microbial robustness in C. glutamicum, such as increased tolerances towards kanamycin, acidic pH and high L-serine, showing its promise and potential for rapid strain improvement. Overall, our study will offer new insights into the understanding of DNA repair and evolutionary adaptation in C. glutamicum.

Demonstration of mid-infrared slow light one-dimensional photonic crystal ring resonator with high-order photonic bandgap.

Integrated mid-infrared sensing offers opportunities for the compact, selective, label-free and non-invasive detection of the absorption fingerprints of many chemical compounds, which is of great scientific and technological importance. To achieve high sensitivity, the key is to boost the interaction between light and analytes. So far, approaches like leveraging the slow light effect, increasing optical path length and enhancing the electric field confinement (f) in the analyte are envisaged. Here, we experimentally investigate a slow light one-dimensional photonic crystal ring resonator operating at high-order photonic bandgap (PBG) in mid-infrared range, which features both strong field confinement in analyte and slow light effect. And the optical path length can also be improved by the resoantor compared with waveguide structure. The characteristics of the first- and second-order bandgap edges are studied by changing the number of patterned periodical holes while keeping other parameters unchanged to confine the bands in the measurement range of our setup between 3.64 and 4.0 µm. Temperature sensitivity of different modes is also experimentally studied, which helps to understand the field confinement. Compared to the fundamental PBG edge modes, the second PBG edge modes show a higher field confinement in the analyte and a comparable group index, leading to larger light-matter interaction. Our work could be used for the design of ultra-sensitive integrated mid-infrared sensors, which have widespread applications including environment monitoring, biosensing and chemical analysis.

Vernier effect-based tunable mid-infrared sensor using silicon-on-insulator cascaded rings.

Vernier effect has been captivated as a promising approach to achieve high-performance photonic sensors. However, experimental demonstration of such sensors in mid-infrared (MIR) range, which covers abundant absorption fingerprints of molecules, is still lacking. Here, we report Vernier effect-based thermally tunable photonic sensors using cascaded ring resonators fabricated on the silicon-on-insulator (SOI) platform. The radii and the coupling gaps in two rings are investigated as key design parameters. By applying organic liquids on our device, we observe an envelope shift of 48 nm with a sensitivity of 3000 nm/RIU and an intensity drop of 6.7 dB. Besides, our device can be thermally tuned with a sensitivity of 0.091 nm/mW. Leveraging the characteristic molecular absorption in the MIR, our work offers new possibilities for complex index sensing, which has wide applications in on-chip photonic sensors.

Improved two-step optimization procedure used for designing an apodizer and Lyot stop in the Lyot coronagraph.

The Lyot coronagraph is a widely known astronomical instrument used to realize direct imaging of exoplanets, and designing transmittance of an apodizer and Lyot stop is the key to obtaining high-contrast imaging. In this paper a new (to the best of our knowledge) optimization procedure used to design the apodizer and Lyot stop in the Lyot coronagraph is proposed. A two-step optimization program is established to obtain the optimum transmittance of an apodizer and Lyot stop in a sequential way. By using the optimized apodizer and Lyot stop obtained through the proposed optimization procedure, both the stellar light and its diffraction light could be strongly suppressed. Numerical results indicate that such an optimized Lyot coronagraph can produce a 1e-10 extinction of the stellar light near the diffraction limit (1.59λ/D), and a high contrast imaging of 1e-07 could still be obtained even with the influence of light intensity of planets themselves. In addition, the two-step optimization procedure brings in two benefits. First, the two-step optimization is approximately 1000 times faster than the joint optimization method [J. Astron. Telesc. Instrum. Syst.2, 011012 (2016)2329-412410.1117/1.JATIS.2.1.011012]. Second, the optimum transmittance of the Lyot stop is binary, and therefore, the requirements of the production process are reduced, resulting in a greatly reduced cost. At the same time, the performance of the optimized Lyot coronagraph is also analyzed in the case of a monochromatic light incident and bandwidth light incident, and the effect of the diameter of the Lyot stop on the results is also discussed in this paper, which makes sense when designing a coronagraph.

Coexistence of air and dielectric modes in single nanocavity.

A deterministic design method and experimental demonstration of single photonic crystal nanocavity supporting both air and dielectric modes in the mid-infrared wavelength region are reported here. The coexistence of both modes is realized by a proper design of photonic dispersion to confine air and dielectric bands simultaneously. By adding central mirrors to make the resonance modes be confined at the bandgap edges, high experimental Q-factors of 2.32 × 104 and 1.59 × 104 are achieved at the resonance wavelength of about 3.875µm and 3.728µm for fundamental dielectric and air modes, respectively. Moreover, multiple sets of air and dielectric modes can be realized by introducing central aperiodic mirrors with multiple bandgaps. The realization of coexistence of air and dielectric modes in single nanocavity will offer opportunities for multifunctional devices, paving the way to integrated multi-parameter sensors, filters, nonlinear devices, and compact light sources.

Thermal annealing study of the mid-infrared aluminum nitride on insulator (AlNOI) photonics platform.

Aluminum nitride on insulator (AlNOI) photonics platform has great potential for mid-infrared applications thanks to the large transparency window, piezoelectric property, and second-order nonlinearity of AlN. However, the deployment of AlNOI platform might be hindered by the high propagation loss. We perform thermal annealing study and demonstrate significant loss improvement in the mid-infrared AlNOI photonics platform. After thermal annealing at 400°C for 2 hours in ambient gas environment, the propagation loss is reduced by half. Bend loss and taper coupling loss are also investigated. The performance of multimode interferometer, directional coupler, and add/drop filter are improved in terms of insertion loss, quality factor, and extinction ratio. Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction spectroscopy suggest the loss improvement is mainly attributed to the reduction of extinction coefficient in the silicon dioxide cladding. Apart from loss improvement, appropriate thermal annealing also helps in reducing thin film stress.

Anomalous plasmon hybridization in nanoantennas near interfaces.

We report on an anomalous plasmon hybridization in side-by-side coupled metallic nanoantennas on top of a silicon waveguide. Contrary to the conventional perception based on Coulomb coupling, the hybridized anti-symmetric mode in our structure possesses a higher resonance frequency than the symmetric mode. This unusual phenomenon reveals a new mechanism of plasmon hybridization, namely, coupling-induced charge redistribution. Our work includes numerical simulation, experimental validation, and theoretical analysis, emphasizing the importance of dielectric interfaces in coupled plasmonic structures, and offers new possibilities for non-Hermitian systems and integrated devices.

Aluminum nitride on insulator (AlNOI) platform for mid-infrared photonics.

We report an aluminum nitride on insulator platform for mid-infrared (MIR) photonics applications beyond 3 µm. Propagation loss and bending loss are studied, while functional devices such as directional couplers, multimode interferometers, and add/drop filters are demonstrated with high performance. The complementary metal-oxide-semiconductor-compatible aluminum nitride offers advantages ranging from a large transparency window, high thermal and chemical resistance, to piezoelectric tunability and three-dimensional integration capability. This platform can have synergy with other photonics platforms to enable novel applications for sensing and thermal imaging in MIR.

Deterministic aperiodic photonic crystal nanobeam supporting adjustable multiple mode-matched resonances.

We investigate nanocavities in deterministic aperiodic photonic crystal (PhC) nanobeams. We reveal that even a single nanocavity can support multiple mode-matched resonances, which show an almost perfect field overlap in the cavity region. The unique property is enabled by the existence of adjustable multiple bandgaps in deterministic aperiodic PhC nanobeams. Our investigation may inspire related studies on low threshold lasers, integrated nonlinear devices, optical filters, and on-chip sensors.

Octave-spanning supercontinuum generation in hybrid silver metaphosphate/silica step-index fibers.

We reveal the potential of step-index fibers consisting of a metaphosphate glass core and a silica cladding as an ultrafast octave-spanning supercontinuum source. The hybrid waveguide was fabricated by pressure-assisted melt filling and possesses a sophisticated dispersion behavior with two zero-dispersion points in the proximity of the Erbium laser bands. The fiber generates an octave-spanning supercontinuum from 0.7 to 2.4 µm if pumped at 1.56 µm with 30 fs pulses and energies as low as 300 pJ. Numerical simulations reveal soliton fission and double dispersive wave generation as the dominant broadening effect. This study highlights phosphate glasses as a promising new candidate for the next generation of broadband photonic devices, as they allow for high rare earth-doping levels and dispersion posttuning via plasmonic nanoparticle growth.

Plasma Proteomic Analysis Based on 4D-DIA Evaluates the Clinical Response to Imrecoxib in the Early Treatment of Osteoarthritis.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary treatment for osteoarthritis (OA), but prolonged use has adverse effects and varying efficacy. Among NSAIDs, imrecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduces side effects yet remains ineffective for half of the patient population. This study aims to identify biomarkers for early evaluation of imrecoxib efficacy in OA for personalized therapy optimization. METHODS: From September 2021 to January 2022, imrecoxib was administered to patients with OA at Nanjing Drum Tower Hospital. Plasma samples from these patients underwent proteomic analysis through the four-dimensional data-independent acquisition (4D-DIA) method, followed by bioinformatics analysis. Potential differentially expressed proteins (DEPs) were validated using enzyme-linked immunosorbent assays (ELISA). RESULTS: Sixty-six patients with knee OA were included and divided into responders (n = 35) and non-responders (n = 31). Proteomic analysis was conducted on 15 patients from each group, with ELISA validation for every patient. We found 140 DEPs between the two groups after imrecoxib treatment, characterized by 29 proteins showing upregulation and 111 displaying downregulation (P < 0.05, fold change > ± 1.2). Galectin-1 (LGALS1), galectin-3 (LGALS3), and cluster of differentiation 44 (CD44) were identified as potential markers for evaluating clinical response to imrecoxib in OA following ELISA validation. CONCLUSION: This study successfully identified biomarkers for evaluating imrecoxib's clinical response in patients with OA using 4D-DIA technology. These biomarkers may play a vital role in future personalized OA treatment strategies, pending further confirmation.

Economic evaluation of camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma in the United States and China.

BACKGROUND: Camrelizumab combined with rivoceranib has been proven effective for treating unresectable hepatocellular carcinoma (uHCC). However, their higher prices than sorafenib could impose a substantial economic burden on patients. AIM: This study aimed to evaluate the relative cost-effectiveness of the combination of camrelizumab and rivoceranib versus sorafenib as first-line therapy for patients with uHCC from the perspective of the US and Chinese payers. METHOD: Using data from the CARES-310 trial, a partitioned survival model (PSM) was developed, considering the perspectives of the US and Chinese payers. The model employed a 15-year time horizon and a biweekly cycle. Direct medical costs and utility data were collected from previous studies and open-access databases. Primary outcomes included quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Price simulations, sensitivity analyses, and subgroup analyses were conducted. RESULTS: The ICER for the US and China was $122,388.62/QALY and $30,410.56/QALY, respectively, falling below the willingness-to-pay (WTP) thresholds of $150,000/QALY for the US and $35,898.87/QALY for China. Price simulations indicated the cost-effectiveness of camrelizumab plus rivoceranib when the price of camrelizumab (200 mg) remained below $6275.19 in the US and $558.09 in China. The primary determinant of cost-effectiveness in both regions was the cost of camrelizumab. CONCLUSION: The combination of camrelizumab and rivoceranib is a cost-effective first-line therapy for uHCC in both the US and China. Lowering their prices could significantly influence their cost-effectiveness and accessibility to patients. These findings will guide clinicians in treating uHCC and help decision-makers formulate value-based drug pricing strategies.

A survey on advancements in image-text multimodal models: From general techniques to biomedical implementations.

With the significant advancements of Large Language Models (LLMs) in the field of Natural Language Processing (NLP), the development of image-text multimodal models has garnered widespread attention. Current surveys on image-text multimodal models mainly focus on representative models or application domains, but lack a review on how general technical models influence the development of domain-specific models, which is crucial for domain researchers. Based on this, this paper first reviews the technological evolution of image-text multimodal models, from early explorations of feature space to visual language encoding structures, and then to the latest large model architectures. Next, from the perspective of technological evolution, we explain how the development of general image-text multimodal technologies promotes the progress of multimodal technologies in the biomedical field, as well as the importance and complexity of specific datasets in the biomedical domain. Then, centered on the tasks of image-text multimodal models, we analyze their common components and challenges. After that, we summarize the architecture, components, and data of general image-text multimodal models, and introduce the applications and improvements of image-text multimodal models in the biomedical field. Finally, we categorize the challenges faced in the development and application of general models into external factors and intrinsic factors, further refining them into 2 external factors and 5 intrinsic factors, and propose targeted solutions, providing guidance for future research directions. For more details and data, please visit our GitHub page: https://github.com/i2vec/A-survey-on-image-text-multimodal-models.

Photogating-assisted tunneling boosts the responsivity and speed of heterogeneous WSe2/Ta2NiSe5 photodetectors.

Photogating effect is the dominant mechanism of most high-responsivity two-dimensional (2D) material photodetectors. However, the ultrahigh responsivities in those devices are intrinsically at the cost of very slow response speed. In this work, we report a WSe2/Ta2NiSe5 heterostructure detector whose photodetection gain and response speed can be enhanced simultaneously, overcoming the trade-off between responsivity and speed. We reveal that photogating-assisted tunneling synergistically allows photocarrier multiplication and carrier acceleration through tunneling under an electrical field. The photogating effect in our device features low-power consumption (in the order of nW) and shows a dependence on the polarization states of incident light, which can be further tuned by source-drain voltages, allowing for wavelength discrimination with just a two-electrode planar structure. Our findings offer more opportunities for the long-sought next-generation photodetectors with high responsivity, fast speed, polarization detection, and multi-color sensing, simultaneously.

Synergistic-potential engineering enables high-efficiency graphene photodetectors for near- to mid-infrared light.

High quantum efficiency and wide-band detection capability are the major thrusts of infrared sensing technology. However, bulk materials with high efficiency have consistently encountered challenges in integration and operational complexity. Meanwhile, two-dimensional (2D) semimetal materials with unique zero-bandgap structures are constrained by the bottleneck of intrinsic quantum efficiency. Here, we report a near-mid infrared ultra-miniaturized graphene photodetector with configurable 2D potential well. The 2D potential well constructed by dielectric structures can spatially (laterally and vertically) produce a strong trapping force on the photogenerated carriers in graphene and inhibit their recombination, thereby improving the external quantum efficiency (EQE) and photogain of the device with wavelength-immunity, which enable a high responsivity of 0.2 A/W-38 A/W across a broad infrared detection band from 1.55 to 11 µm. Thereafter, a room-temperature detectivity approaching 1 × 109 cm Hz1/2 W-1 is obtained under blackbody radiation. Furthermore, a synergistic effect of electric and light field in the 2D potential well enables high-efficiency polarization-sensitive detection at tunable wavelengths. Our strategy opens up alternative possibilities for easy fabrication, high-performance and multifunctional infrared photodetectors.

Synchronous embedded growth of Mo2C nanodisk arrays immobilized on porous carbon nanosheets for ultra-stable sodium storage.

Sodium ion capacitors (SICs) that combine the merits of both rechargeable batteries and supercapacitors have gained widespread recognition for their high energy density and extended cycle life as new energy storage devices. However, the purposeful design of advanced battery-type anodes has become an urgent need to remedy the dynamics mismatch with the capacitive cathode. Herein, we propose a simple but efficient bottom-up approach to build three-dimensional Mo2C/C hybrid architectures in situ as anodes for SICs. By finely regulating the ratio of carbon and molybdenum sources, the optimized Mo2C/C, where even thinner subunit assembled Mo2C nanodisk (∼47.1 nm in thickness) arrays are immobilized on carbon nanosheet substrate via the synchronous embedded growth, rapid electron and ion diffusion/transport expressways, abundant active sites and robust structural stability were achieved for efficient sodium storage. Benefiting from the synergistic contributions of the components, the optimum Mo2C/C anode displays an outstanding rate and long-cycle properties as a competitive anode. Moreover, the constructed Mo2C/C-based SICs exhibited an energy density of ∼16.7 W h kg-1 at 10 kW h kg-1, along with ∼22.5% capacitance degradation over 4000 cycles at 1 A g-1. This contribution will guide the precise synthesis of other versatile Mo2C-based hybrids towards energy-related applications and beyond.

Cost-Effectiveness Analysis of Tislelizumab Plus Chemotherapy as First-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma in China.

Background: Tislelizumab plus chemotherapy improved overall survival compared to chemotherapy alone, while maintaining an acceptable level of safety. But it's still unclear which strategy is the most cost-effective. The objective of the study was to compare the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) versus chemotherapy alone. Methods: A partitioned survival model with three states was constructed based on the RATIONALE-306 trial. The model's time horizon was ten years, and its cycle was three weeks. Only direct medical costs were considered from the healthcare perspective in China. Calculations were performed on total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity and probabilistic sensitivity analysis (PSA) were performed to determine the uncertainty regarding model parameters. Results: Tislelizumab plus chemotherapy provided 1.35 QALYs for $26,450.77, while chemotherapy alone provided 0.89 QALY for $16,687.15. Compared to chemotherapy alone, tislelizumab had an ICER of $21,062.09/QALY. At the threshold of three times the Chinese GDP per capita ($38,253/QALY), the PSA indicated that tislelizumab had a 96.4% likelihood of being designated cost-effective. At the threshold of 1.5 times the Chinese GDP per capita ($19,126.5/QALY), the PSA indicated that tislelizumab had a probability of 48.7% of being designated cost-effective. Conclusion: Tislelizumab plus chemotherapy as the first treatment for patients with advanced or metastatic ESCC may be a cost-effective option compared to chemotherapy alone at 3 times Chinese GDP per capita.

Predictive Factors for Acute Postoperative Pain After Open Radical Gastrectomy for Gastric Cancer.

Background: Pain has become an important factor in evaluating patients' quality of life and clinical treatment. For gastric cancer (GC) patients, open radical gastrectomy (OG) causes significant trauma to the body, increases patients' pain after operation, and delays early recovery. The aim of this study was to investigate the predictive factors of acute pain after OG within postoperative 72 h. Methods: From March 2020 to September 2021, 307 patients who underwent OG were included in the study in Nanjing Drum Tower Hospital. The predictors included demographic predictors, pathological data, surgical predictors, and intraoperative predictors. The pain scores at 12, 24, 48, and 72 h after operation were evaluated by numeric rating scale (NRS). The predictors of acute pain were determined by univariate and multivariate analysis. Results: The average pain score (NRS) of patients showed a downward trend over time within 72 h after OG. Multivariate analysis indicated that total gastrectomy (OR 1.823, 95% CI 1.094-3.040, P < 0.05), AJCC TNM stage (II) (OR.232, 95% CI 0.062-0.872, P < 0.05), AJCC TNM stage(III) (OR.185, 95% CI 0.049-0.698, P < 0.05), BMI (kg/m2) (OR 1.75, 95% CI 1.029-2.976, P < 0.05), distant metastasis (OR 3.054, 95% CI 1.019-9.155, P < 0.05), intraoperative transfusion (OR 2.246, 95% CI 1.267-3.982, P < 0.01) were significant predictive factors for acute pain after OG. Conclusion: Reasonable postoperative acute pain control was the prerequisite for accelerating the postoperative rehabilitation of patients. In order to reduce the occurrence of excessive or insufficient analgesia, it was necessary for patients who underwent OG to formulate appropriate analgesics according to risk factors.