Identification of RoCYP01 (CYP716A155) enables construction of engineered yeast for high-yield production of betulinic acid

Betulinic acid (BA) and its derivatives possess potent pharmacological activity against cancer and HIV. As with many phytochemicals, access to BA is limited by the requirement for laborious extraction from plant biomass where it is found in low amounts. This might be alleviated by metabolically engineering production of BA into an industrially relevant microbe such as Saccharomyces cerevisiae (yeast), which requires complete elucidation of the corresponding biosynthetic pathway. However, while cytochrome P450 enzymes (CYPs) that can oxidize lupeol into BA have been previously identified from the CYP716A subfamily, these generally do not seem to be specific to such biosynthesis and, in any case, have not been shown to enable high-yielding metabolic engineering. Here RoCYP01 (CYP716A155) was identified from the BA-producing plant Rosmarinus officinalis (rosemary) and demonstrated to effectively convert lupeol into BA, with strong correlation of its expression and BA accumulation. This was further utilized to construct a yeast strain that yields \u3e 1 g/L of BA, providing a viable route for biotechnological production of this valuable triterpenoid

Applications of various range shifters for proton pencil beam scanning radiotherapy

Background A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors. Methods Three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system. Results A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body. Conclusion We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB

Four Eremophilane Sesquiterpenes from the Mangrove Endophytic Fungus Xylaria sp. BL321

Three new eremophilane sesquiterpenes (1–3) were isolated from the mangrove endophytic fungus Xylaria sp. BL321 together with 07H239-A (4), a known analogue of the new compounds. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. Compound 4 showed activation activity on α-glucosidase at 0.15 μM (146%), and then, 4 gradually produced inhibitory activity on α-glucosidase with increasing concentration, and the IC50 value is 6.54 μM

Latissimus dorsi flap – the main force in breast reconstruction for breast tumor in Chinese population

BackgroundThe latissimus dorsi flap (LDF) is the most commonly used autologous flap for breast reconstruction (BR) in China. We conducted this study to explore the current status of BR using LDF with/without implants.MethodsThis study was a single-center retrospective study that included breast tumor patients who underwent LDF breast reconstruction at Fudan University Shanghai Cancer Center (FUSCC) between 2000 and 2021.ResultsWe analyzed 4918 patients who underwent postmastectomy BR, including 1730 patients (35.2%) with autologous flaps. LDF was used for BR in 1093 (22.2%) patients, and an abdominal flap was used in 637 (13.0%) patients. The proportion of LDFs used in autologous BR patients decreased each year and dropped to approximately 65.0% after 2013 due to the increased use of abdominal flaps. Among these patients, 609 underwent extended LDF (ELDF) BR, 455 underwent LDF BR with implants, and 30 received a LDF as a salvage flap due to previous flap or implant failure. Patients who underwent ELDF reconstruction were older and had a higher BMI than those who received a LDF with implants. There was no significant difference in the mean postoperative hospital stay, neoadjuvant chemotherapy rates, or adjuvant radiotherapy rates between the two groups. Major complications requiring surgical intervention occurred in 25 patients (2.29%). There was no significant difference in the incidence of major complications between the two groups (P=0.542).ConclusionsLDF breast reconstruction is a well-developed and safe procedure. The duration of postoperative hospitalization nor the incidence of major complications was affected by implant use

Impacts of systemic inflammation response index on the prognosis of patients with ischemic heart failure after percutaneous coronary intervention

BackgroundAtherosclerosis and cardiovascular diseases are significantly affected by low-grade chronic inflammation. As a new inflammatory marker, the systemic inflammation response index (SIRI) has been demonstrated to be associated with several cardiovascular disease prognoses. This study aimed to investigate the prognostic impact of SIRI in individuals having ischemic heart failure (IHF) following percutaneous coronary intervention (PCI).MethodsThis observational, retrospective cohort study was conducted at a single site. Finally, the research involved 1,963 individuals with IHF who underwent PCI, with a 36-month follow-up duration. Based on the SIRI quartiles, all patients were classified into four groups. Major adverse cardiovascular events (MACEs) were the primary outcomes. Every element of the main endpoint appeared in the secondary endpoints: all-cause mortality, non-fatal myocardial infarction (MI), and any revascularization. Kaplan–Meier survival analysis was conducted to assess the incidence of endpoints across the four groups. Multivariate Cox proportional hazards analysis confirmed the independent impact of SIRI on both the primary and secondary endpoints. The restricted cubic spline (RCS) was used to assess the nonlinear association between the SIRI and endpoints. Subgroup analysis was performed to confirm the implications of SIRI on MACE in the different subgroups.ResultsThe main outcome was much more common in patients with a higher SIRI. The Kaplan–Meier curve was another tool that was used to confirm the favorable connection between SIRI and MACE. SIRI was individually connected to a higher chance of the main outcome according to multivariate analyses, whether or not SIRI was a constant [SIRI, per one−unit increase, hazard ratio (HR) 1.04, 95% confidence interval (95% CI) 1.01–1.07, p = 0.003] or categorical variable [quartile of SIRI, the HR (95% CI) values for quartile 4 were 1.88 (1.47–2.42), p <0.001, with quartile 1 as a reference]. RCS demonstrated that the hazard of the primary and secondary endpoints generally increased as SIRI increased. A non-linear association of SIRI with the risk of MACE and any revascularization (Non-linear P <0.001) was observed. Subgroup analysis confirmed the increased risk of MACE with elevated SIRI in New York Heart Association (NYHA) class III–IV (P for interaction = 0.005).ConclusionIn patients with IHF undergoing PCI, increased SIRI was a risk factor for MACE independent of other factors. SIRI may represent a novel, promising, and low-grade inflammatory marker for the prognosis of patients with IHF undergoing PCI

Baiji genomes reveal low genetic variability and new insights into secondary aquatic adaptations

The baiji, or Yangtze River dolphin (Lipotes vexillifer), is a flagship species for the conservation of aquatic animals and ecosystems in the Yangtze River of China; however, this species has now been recognized as functionally extinct. Here we report a high-quality draft genome and three re-sequenced genomes of L. vexillifer using Illumina short-read sequencing technology. Comparative genomic analyses reveal that cetaceans have a slow molecular clock and molecular adaptations to their aquatic lifestyle. We also find a significantly lower number of heterozygous single nucleotide polymorphisms in the baiji compared to all other mammalian genomes reported thus far. A reconstruction of the demographic history of the baiji indicates that a bottleneck occurred near the end of the last deglaciation, a time coinciding with a rapid decrease in temperature and the rise of eustatic sea level

Digital Integration of LiDAR System Implemented in a Low-Cost FPGA

With the development of artificial intelligence, LiDAR finds significant applications in robotics and autonomous driving. Aiming at increasing the compactness and the integration of 2-D LiDAR, this paper presents a highly digitally integrated 2-D LiDAR system implemented in a low-cost FPGA. The system is made of off-the-shelf components to limit the cost to USD 100. A laser transceiver with a symmetrical transmitting and receiving lens emits and collects laser pulses to range distance using the time-of-flight (ToF) method. As a key component in ToF, the FPGA-based time-to-digital converter (TDC) is adopted for counting the round-trip time of pulses, which is implemented in a low-cost FPGA of ZYNQ7010 with limited resources. The symmetrical structure of the delay line is used to design a more efficient TDC. The FPGA-TDC enables flexibility of design and integration with more functional logics and is microcontroller-free. All the digital logics including data processing and controlling are integrated into an FPGA with the TDC logics to realize fully digital integration and compact dimensions. The utilization of the whole architecture in the FPGA is about 15%. The experimental results demonstrated that the ranging accuracy of the LiDAR is about 2 cm, which is suitable for consumer electronics

Digital Integration of LiDAR System Implemented in a Low-Cost FPGA

With the development of artificial intelligence, LiDAR finds significant applications in robotics and autonomous driving. Aiming at increasing the compactness and the integration of 2-D LiDAR, this paper presents a highly digitally integrated 2-D LiDAR system implemented in a low-cost FPGA. The system is made of off-the-shelf components to limit the cost to USD 100. A laser transceiver with a symmetrical transmitting and receiving lens emits and collects laser pulses to range distance using the time-of-flight (ToF) method. As a key component in ToF, the FPGA-based time-to-digital converter (TDC) is adopted for counting the round-trip time of pulses, which is implemented in a low-cost FPGA of ZYNQ7010 with limited resources. The symmetrical structure of the delay line is used to design a more efficient TDC. The FPGA-TDC enables flexibility of design and integration with more functional logics and is microcontroller-free. All the digital logics including data processing and controlling are integrated into an FPGA with the TDC logics to realize fully digital integration and compact dimensions. The utilization of the whole architecture in the FPGA is about 15%. The experimental results demonstrated that the ranging accuracy of the LiDAR is about 2 cm, which is suitable for consumer electronics

Sensitivities of Fall Armyworm (<i>Spodoptera frugiperda</i>) Populations in Different Regions of China to Four Bt Proteins

Fall armyworm (FAW), Spodoptera frugiperda, invaded the south of China in December 2018 and has since posed a huge threat to crop production in China. However, transgenic Bacillus thuringiensis (Bt) corn can efficiently control the damage caused by FAWs. In fact, the Chinese government has issued biosafety certificates for several Bt corn hybrids expressing any one of four Bt proteins, Vip3A, Cry1F, Cry1Ab, and Cry2Ab, or combinations thereof, to control FAWs. These Bt corn events are soon to be commercialized in China. Therefore, it is necessary to monitor and evaluate whether the FAW has developed resistance to any of the Bt corn hybrids planted in fields in China. To address this issue, we collected 11 geographical populations of FAWs and determined the sensitivity of each to the aforementioned four purified Bt proteins as assessed by diet surface overlay bioassays. The ranges for the 50% lethal concentration (LC50) of the four Bt proteins to all FAW populations were as follows: 11.42–88.33 ng/cm2 (for Vip3A), 111.21–517.33 (Cry1F), 135.76–1108.47 (Cry1Ab), and 994.42–5492.50 (Cry2Ab). The corresponding ranges for the 50% growth inhibition concentrations (GIC50) were 1.43–14.86, 2.35–138.97, 1.58–464.86, and 25.01–1266.07 ng/cm2. The lethal effects and growth inhibition effects of the four Bt proteins on FAW were in the same order of Vip3A > Cry1F > Cry1Ab > Cry2Ab. A comparison with published LC50 values of Bt proteins towards sensitive FAW populations revealed that all 11 FAW populations in this study were sensitive to Vip3A, Cry1F, and Cry1Ab. This study provides foundational data for monitoring and controlling the resistance of Bt corn to FAW in China