Slow-Light-Enhanced Polarization Division Multiplexing Infrared Absorption Spectroscopy for On-Chip Wideband Multigas Detection in a 1D Photonic Crystal Waveguide.

Slow-light photonic crystal waveguide (PCW) gas sensors based on infrared absorption spectroscopy play a pivotal role in enhancing the on-chip interaction between light and gas molecules, thereby significantly boosting sensor sensitivity. However, two-dimensional (2D) PCWs are limited by their narrow mode bandwidth and susceptibility to polarization, which restricts their ability for multigas measurement. Due to quasi-TE and quasi-TM mode guiding characteristics in one-dimensional (1D) PCW, a novel slow-light-enhanced polarization division multiplexing infrared absorption spectroscopy was proposed for on-chip wideband multigas detection. The optimized 1D PCW gas sensor experimentally shows an impressive slow-light mode bandwidth exceeding 100 nm (TM, 1500-1550 nm; TE, 1610-1660 nm) with a group index ranging from 4 to 25 for the two polarizations. The achieved bandwidth in the 1D PCW is 2-3 times that of the reported quasi-TE polarized 2D PCWs. By targeting the absorption lines of different gas species, multigas detection can be realized by modulating the lasers and demodulating the absorption signals at different frequencies. As an example, we performed dual-gas measurements with the 1D PCW sensor operating in TE mode at 1.65 µm for methane (CH4) detection and in TM mode at 1.53 µm for acetylene (C2H2) detection. The 1 mm long sensor achieved a remarkable limit of detection (LoD) of 0.055% for CH4 with an averaging time of 17.6 s, while for C2H2, the LoD was 0.18%. This polarization multiplexing sensor shows great potential for on-chip gas measurement because of the slow-light enhancement in the light-gas interaction effect as well as the large slow-light bandwidth for multigas detection.

Mid-infrared auto-correction on-chip waveguide gas sensor based on 2f/1f wavelength modulation spectroscopy.

Compared to the most commonly used on-chip direct absorption spectroscopy (DAS) gas detection technique, the second harmonic (2f) based on-chip wavelength modulation spectroscopy (WMS) proposed by our group has the faculty to suppress noise and improve performance, but the accuracy of 2f WMS is easily affected by optical power variation. A mid-infrared auto-correction on-chip gas sensor based on 2f/1f WMS was proposed for decreasing the influence of the variation of optical power. The limit of detection of methane (CH4) obtained by a chalcogenide waveguide with a length of 10 mm is 0.031%. Compared with the 2f WMS, the maximum relative concentration error of the auto-correction on-chip gas sensor was decreased by ∼5.6 times. The measurement error is ≤2% in a temperature variation range of 30°C. This auto-correction sensor without a complicated manual calibration is helpful to the high accuracy measurement for on-chip integrated gas sensing.

Polyarene Oxides with Tunable Quinone Units for Photocatalytic CO2 Reduction: A Simple Strategy toward Effective and Selective Catalysts.

The photocatalytic transformation of carbon dioxide (CO2) into valuable chemicals is a challenging process that requires effective and selective catalysts. However, most polymer-based photocatalysts with electron donor-acceptor (D-A) structures are synthesized with a fixed D-A ratio by using expensive monomers. Herein, we report a simple strategy to prepare polyarene oxides (PAOs) with quinone structural units via oxidation treatment of polyarene (PA). The resultant PAOs show tunable D-A structures and electronic band positions depending on the degree of oxidation, which can catalyze the photoreduction of CO2 with water under visible light irradiation, generating CO as the sole carbonaceous product without H2 generation. Especially, the PAO with an oxygen content of 17.6% afforded the highest CO production rate of 161.9 µmol g-1 h-1. It is verified that the redox transformation between quinone and phenolic hydroxyl in PAOs achieves CO2 photoreduction coupled with water oxidation. This study provides a facile way to access conjugated polymers with a tunable D-A structure and demonstrates that the resultant PAOs are promising photocatalysts for CO2 reduction.

Risk factors for low back pain in the Chinese population: a systematic review and meta-analysis.

BACKGROUND: In China, the world's largest developing country, low back pain (LBP) is a common public health issue affecting workability. This meta-analysis aimed to systematically assess the risk factors of LBP in the Chinese population. METHODS: Four English language and four Chinese databases were searched, and cross-sectional studies on the risk factors for LBP in Chinese populations were identified and collected. The search timeframe covered the period from the establishment of the database to November 2023. Two researchers independently reviewed the literature, extracted the data, and evaluated the risk of bias. Begg's and Egger's tests were used to evaluate publication bias. RESULTS: Fifteen cross-sectional studies involving 86,575 people were included. Seven risk factors for LBP were identified. Six risk factors were statistically significant: Cigarette smoking (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.15, 2.08, P = 0.004, I2 = 72%), body mass index (BMI) ≥ 28 kg/m² (OR = 4.51; 95% CI: 3.36, 6.07, P < 0.00001, I2 = 8%), female sex (OR = 1.54; 95% CI: 1.25, 1.90, P < 0.0001, I2 = 63%), vibration exposure at work (OR = 1.65; 95% CI: 1.16, 2.34, P = 0.006, I2 = 84%), working overtime (OR = 2.57; 95% CI: 1.12, 5.91, P = 0.03, I2 = 85%), and lack of exercise (OR = 2.48; 95% CI: 1.62, 3.78, P < 0.0001, I2 = 0%). One risk factor that was not statistically significant was standing for long periods (OR = 1.02; 95% CI: 0.82, 1.26, P = 0.88, I2 = 73%). CONCLUSIONS: This study found that smoking, a BMI ≥ 28 kg/m², female sex, vibration exposure at work, working overtime, and lack of exercise may be risk factors for LBP in the Chinese population. Because the included studies were cross-sectional and the certainty of the evidence was very low, the results need to be interpreted cautiously. Multicentre, high-quality studies should be conducted in the future. To reduce the prevalence of LBP, the Chinese government and hospitals must develop early screening programs and implement effective preventive and interventional measures. TRIAL REGISTRATION: This study is registered in the PROSPERO database (No. CRD42023447857).

Vaginal flora in HPV infection: a cross­sectional analysis.

OBJECTIVE: The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with HPV infection and to analyse the changes in the vaginal flora and enzyme profiles in females with HPV infection. METHODS: We conducted a cross-sectional study involving 206 participants who underwent HPV genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The vaginal microbial communities of both groups were analysed for diversity and differences to explore their association with HPV infection. RESULTS: The abundance of Lactobacillus was found to be reduced, while Gardnerella vaginalis was significantly more prevalent in the HPV + group. In terms of alpha diversity indices, the Shannon index (P = .0036) and Simpson index (P = .02) were higher in the HPV + group compared to the HPV - group, indicating greater community diversity in the HPV + group. Among the 10 sexually transmitted diseases pathogens analysed, Uup3 and Uup6 were significantly associated with HPV infection. Statistically significant differences were observed in Nugent scores and bacterial vaginosis between the two groups (P < .05). In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group. CONCLUSION: Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of Lactobacillus, increased prevalence of Gardnerella, and abnormal enzyme profiles are closely linked to HPV infection.

The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with human papillomavirus infection and to analyse the changes in the vaginal flora and enzyme profiles in females with human papillomavirus infection. We conducted a cross-sectional study involving 206 participants who underwent human papillomavirus genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The abundance of Lactobacillus was found to be reduced, while Gardnerella vaginalis was significantly more prevalent in the HPV + group. In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group. Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of Lactobacillus, increased prevalence of Gardnerella, and abnormal enzyme profiles are closely linked to HPV infection.

SOCS1 acts as a ferroptosis driver to inhibit the progression and chemotherapy resistance of triple-negative breast cancer.

OBJECTIVES: Ferroptosis is involved in many types of cancers, including triple-negative breast cancer (TNBC). Suppressor of cytokine signaling 1 (SOCS1) has recently been implicated as a regulator of ferroptosis. We aim to explore whether targeting SOCS1 is a potential therapeutic strategy for TNBC therapy. METHODS: Stable cell lines were constructed using lentivirus transfection. Cell viability was determined using CCK-8 and cell colony formation assays, respectively. Assays including lactate dehydrogenase release, lipid peroxidation and malondialdehyde assays were conducted to evaluate ferroptosis. Real-time quantitative polymerase chain reaction and western blotting were performed to evaluate mRNA and protein expression, respectively. A xenograft animal model was established by subcutaneous injection of cells into the flank. RESULTS: Our results showed that SOCS1 overexpression inhibited cell proliferation and induced ferroptosis in TNBC cells, while SOCS1 knockdown promoted cell proliferation and reduced ferroptosis. We also found that SOCS1 regulated ferroptosis by modulating GPX4 expression. Furthermore, SOCS1 regulated cisplatin resistance in TNBC cells by promoting ferroptosis. Our in vivo data suggested that SOCS1 regulated tumor growth and cisplatin resistance in vivo. CONCLUSIONS: SOCS1 inhibits the progression and chemotherapy resistance of TNBC by regulating GPX4 expression.

Superhydrophobic Thermoplastic Polyurethane Foam Fabricated by Phase Separation and Silica Coating for Oil-Water Separation.

Oil spills and the presence of oily wastewater have resulted in substantial ecological damage. Superhydrophobic polymer foam with selectivity and adsorption capacity is a promising candidate for efficient oil-water separation. In this study, a method that combines phase separation and silica coating to produce superhydrophobic thermoplastic polyurethane (TPU) foam is proposed. The TPU foam demonstrates superhydrophobicity with a water contact angle of 155.62°, and exhibits a maximum saturated adsorption capacity of 54.11 g g-1 . Furthermore, the foam can be utilized as a filter for oil-water separation, maintaining its filtration efficiency (41.2 m3  m2  h-1 ) even after ten filtration cycles.

Sex-specific relationships between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort.

Birth weight is an indicator linking intrauterine environmental exposures to later-life diseases, and intrauterine metal exposure may affect birth weight in a sex-specific manner. We investigated sex-specific associations between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort. The birth weight of 1296 boys and 1098 girls were recorded, and 10 metals in maternal urine samples collected during pregnancy were measured using inductively coupled plasma mass spectrometry. Bayesian Kernel Machine Regression was used to estimate the association of individual metals or metal mixtures and birth weight for gestational age (BW for GA). The model showed a sex-specific relationship between prenatal exposure to metal mixtures and BW for GA with a significant negative association in girls and a non-significant positive association in boys. Cadmium (Cd) and nickel (Ni) were positively and negatively associated with BW for GA in girls, respectively. Moreover, increasing thallium (Tl) concentration lowered the positive association between Cd and BW for GA and enhanced the negative association between Ni and BW for GA in girls. When exposure to other metals increased, the positive association with Cd diminished, whereas the negative association with Ni or Tl increased. Our findings provide evidence supporting the complex effects of intrauterine exposure to metal mixtures on the birth weight of girls and further highlight the sex heterogeneity in fetal development influenced by intrauterine environmental factors.

An Improved YOLOv7 Lightweight Detection Algorithm for Obscured Pedestrians.

The detection algorithm commonly misses obscured pedestrians in traffic scenes with a high pedestrian density because mutual occlusion among pedestrians reduces the prediction box score of the concealed pedestrians. The paper uses the YOLOv7 algorithm as the baseline and makes the following three improvements by investigating the variables influencing the detection method's performance: First, the backbone network of the YOLOv7 algorithm is replaced with the lightweight feature extraction network Mobilenetv3 since the pedestrian detection algorithm frequently needs to be deployed in driverless mobile, which requires a fast operating speed of the algorithm; second, a high-resolution feature pyramid structure is suggested for the issue of missed detection of hidden pedestrians, which upscales the feature maps generated from the feature pyramid to increase the resolution of the output feature maps and introduces shallow feature maps to strengthen the distinctions between adjacent sub-features to enhance the network's ability to extract features for the visible area of hidden pedestrians and small-sized pedestrians in order to produce deeper features with greater differentiation for pedestrians; and the third is to suggest a detection head based on an attention mechanism that is employed to lower the confidence level of target neighboring sub-features, lower the quantity of redundant detection boxes, and lower the following NMS computation. The mAP of the suggested approach in this work achieves 89.75%, which is 9.5 percentage points better than the YOLOv7 detection algorithm, according to experiments on the CrowdHuman pedestrian-intensive dataset. The algorithm proposed in this paper can considerably increase the detection performance of the detection algorithm, particularly for obscured pedestrians and small-sized pedestrians in the dataset, according to the experimental effect plots.

Highly Activated Neuronal Firings Monitored by Implantable Microelectrode Array in the Paraventricular Thalamus of Insomnia Rats.

Insomnia is a common sleep disorder around the world, which is harmful to people's health, daily life, and work. The paraventricular thalamus (PVT) plays an essential role in the sleep-wake transition. However, high temporal-spatial resolution microdevice technology is lacking for accurate detection and regulation of deep brain nuclei. The means for analyzing sleep-wake mechanisms and treating sleep disorders are limited. To detect the relationship between the PVT and insomnia, we designed and fabricated a special microelectrode array (MEA) to record electrophysiological signals of the PVT for insomnia and control rats. Platinum nanoparticles (PtNPs) were modified onto an MEA, which caused the impedance to decrease and improved the signal-to-noise ratio. We established the model of insomnia in rats and analyzed and compared the neural signals in detail before and after insomnia. In insomnia, the spike firing rate was increased from 5.48 ± 0.28 spike/s to 7.39 ± 0.65 spike/s, and the power of local field potential (LFP) decreased in the delta frequency band and increased in the beta frequency band. Furthermore, the synchronicity between PVT neurons declined, and burst-like firing was observed. Our study found neurons of the PVT were more activated in the insomnia state than in the control state. It also provided an effective MEA to detect the deep brain signals at the cellular level, which conformed with macroscopical LFP and insomnia symptoms. These results laid the foundation for studying PVT and the sleep-wake mechanism and were also helpful for treating sleep disorders.

Deep Learning for Detection of Intracranial Aneurysms from Computed Tomography Angiography Images.

The accuracy of computed tomography angiography (CTA) image interpretation depends on the radiologist. This study aims to develop a new method for automatically detecting intracranial aneurysms from CTA images using deep learning, based on a convolutional neural network (CNN) implemented on the DeepMedic platform. Ninety CTA scans of patients with intracranial aneurysms are collected and divided into two datasets: training (80 subjects) and test (10 subjects) datasets. Subsequently, a deep learning architecture with a three-dimensional (3D) CNN model is implemented on the DeepMedic platform for the automatic segmentation and detection of intracranial aneurysms from the CTA images. The samples in the training dataset are used to train the CNN model, and those in the test dataset are used to assess the performance of the established system. Sensitivity, positive predictive value (PPV), and false positives are evaluated. The overall sensitivity and PPV of this system for detecting intracranial aneurysms from CTA images are 92.3% and 100%, respectively, and the segmentation sensitivity is 92.3%. The performance of the system in the detection of intracranial aneurysms is closely related to their size. The detection sensitivity for small intracranial aneurysms (≤ 3 mm) is 66.7%, whereas the sensitivity of detection for large (> 10 mm) and medium-sized (3-10 mm) intracranial aneurysms is 100%. The deep learning architecture with a 3D CNN model on the DeepMedic platform can reliably segment and detect intracranial aneurysms from CTA images with high sensitivity.

Aspartate ß-Hydroxylase Serves as a Prognostic Biomarker for Neoadjuvant Chemotherapy in Gastric Cancer.

Neoadjuvant chemotherapy (NACT) has been established as being an effective treatment for advanced gastric cancer (GC), while the predictive biomarker of NACT efficacy remains under investigation. Aspartate ß-hydroxylase (ASPH) represents an attractive target which is a highly conserved transmembrane enzyme overexpressed in human GC, and participates in the malignant transformation by promoting tumor cell motility. Here, we evaluated the expression of ASPH by immunohistochemistry in 350 GC tissues (including samples for NACT) and found that ASPH expression was higher in patients undergoing NACT compared with patients without NACT pre-operation. The OS and PFS time of ASPH-intensely positive patients was significantly shorter than that of the negative patients in the NACT group, while the difference was not significant in patients without NACT. We showed that ASPH knockout enhanced the inhibitory effects of chemotherapeutic drugs on the cell proliferation, migration, and invasion in vitro and suppressed tumor progression in vivo. Co-immunoprecipitation revealed that ASPH might interact with LAPTM4B to perform chemotherapeutic drug resistance. Our results suggested that ASPH might serve as a candidate biomarker to predict prognosis and a novel therapeutic target for gastric cancer patients treated with neoadjuvant chemotherapy.

Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

Development of a mid-infrared sensor system for early fire identification in cotton harvesting operations.

To realize early fire identification in cotton harvesting operations, a mid-infrared carbon monoxide (CO) sensor system was developed. To match the broadband light source with a 15° divergence angle, a multipass gas cell (MPGC) with an effective path length of 180 cm was designed to improve sensor sensitivity, leading to a limit of detection (LoD) of 0.83 parts-per-million by volume (ppmv). A damping module with springs at the bottom and front/back sides was fabricated, which can effectively reduce the vibration intensity by >80%. The sensor system can operate normally from -40 °C to 85 °C by stabilizing the temperature of the optical module through heating or cooling as well as using automotive electronic components. An adaptive early fire identification algorithm based on a dual-parameter threshold alarming method was proposed to avoid false and missing alarms. Field deployments on a harvester verified the good practicability of the sensor system.

Optimized tools and timing of response reassessment after neoadjuvant chemoradiation in rectal cancer.

PURPOSE: Reassessment tools of response to long-course neoadjuvant chemoradiation treatment (nCRT) in patients with locally advanced rectal cancer (LARC) are important in predicting complete response (CR) and thus deciding whether a wait-and-watch strategy can be implemented in these patients. Choosing which routine reassessment tools are optimal and when to use them is still unclear and will be researched in the study. METHODS: Altogether, 250 patients with LARC who received nCRT from 2013 to 2021 and were followed up were retrospectively reviewed. Common reassessment tools of response included digital rectal examination (DRE), clinical examination and symptoms, endoscopy, biopsy, magnetic resonance imaging (MRI), and blood biomarkers. RESULTS: Overall, 27.20% (68/250) patients had a complete response and 72.80% (182/250) did not. The combination of MRI, endoscopy, and biopsy showed the best performance in terms of accuracy of 74% and area under the curve (AUC, 0.714, 95% CI 0.546-0.882). Reassessing through DRE and presence of symptoms failed to improve the efficacy of response reassessment. After 100 days, biopsy as an assessment tool would obtain a substantial rise in accuracy from 51.28 to 100% (p = 0.003). CONCLUSION: The combination of MRI, endoscopy, and biopsy is suitable as the reassessment tool of response for applying a wait-and-watch strategy after long-course nCRT in patients with LARC. The accuracy of biopsy as reassessment tools would be improved if they were used over 100 days after nCRT in patients with rectal cancer.

Correction: Wang et al. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Molecules 2018, 23, 391.

The authors would like to correct an error in the original publication [...].

Light-induced off-axis cavity-enhanced thermoelastic spectroscopy in the near-infrared for trace gas sensing.

A trace gas sensing technique of light-induced off-axis cavity-enhanced thermoelastic spectroscopy (OA-CETES) in the near-infrared was demonstrated by combing a high-finesse off-axis integrated cavity and a high Q-factor resonant quartz tuning fork (QTF). Sensor parameters of the cavity and QTF were optimized numerically and experimentally. As a proof-of-principle, we employed the OA-CETES for water vapor (H2O) detection using a QTF (Q-factor ∼12000 in atmospheric pressure) and a 10cm-long Fabry-Perot cavity (finesse ∼ 482). By probing a H2O line at 7306.75 cm-1, the developed OA-CETES sensor achieved a minimum detection limit (MDL) of 8.7 parts per million (ppm) for a 300 ms integration time and a normalized noise equivalent absorption (NNEA) coefficient of 4.12 × 10-9cm-1 WHz-1/2. Continuous monitoring of indoor and outdoor atmospheric H2O concentration levels was performed for verifying the sensing applicability. The realization of the proposed OA-CETES technique with compact QTF and long effective path cavity allows a class of optical sensors with low cost, high sensitivity and potential for long-distance and multi-point sensing.

Mid-infrared ChG-on-MgF2 waveguide gas sensor based on wavelength modulation spectroscopy: publisher's note.

This publisher's note contains corrections to Opt. Lett.46, 4797 (2021)OPLEDP0146-959210.1364/OL.440361.

Mid-infrared ChG-on-MgF2 waveguide gas sensor based on wavelength modulation spectroscopy.

A novel, to the best of our knowledge, mid-infrared chalcogenide (ChG) on magnesium fluoride (MgF2) waveguide gas sensor was fabricated by using the lift-off method. MgF2 was used as a lower cladding layer to increase the external confinement factor for enhancing light-gas interaction. Wavelength modulation spectroscopy (WMS) was used in carbon dioxide (CO2) detection at the wavelength of 4319 nm (2315.2cm-1). The limit of detection for the 1-cm-long sensing waveguide based on WMS is ∼0.3%, which is >8 times lower than the same sensor using direct absorption spectroscopy (DAS). The combination of WMS with the waveguide gas sensor provides a new measurement scheme for the performance improvement of on-chip gas detection.

STEP® vectors for rapid generation of stable transfected CHO cell pools and clones with high expression levels and product quality homogeneity of difficult-to-express proteins.

Many proteins produced in CHO cells need evaluation for their clinical and commercial potential. Traditional methods based on stable clone generation are slow and unsuitable for screening larger numbers of proteins, while transient expression technologies are fast but unpredictable regarding product quality and lacking an optional path to subcloning. The STEP® vector technology introduced here combines the best properties of both methods. STEP® vectors contain a strong transcriptional cassette driving expression of a bicistronic mRNA. The gene-of-interest (GOI) is cloned upstream of a functionally impaired zeocin resistance gene (FI-Zeo) whose translation is coupled to that of the GOI through an IRES. Stable transfected cells surviving zeocin selection produce high levels of FI-Zeo and thus, high levels of the GOI-encoded protein. By using different spacers, the translational coupling efficiency and selection strength can be controlled allowing maximization of expression of any GOI. Production of laronidase and factor VII (FVII) is presented as examples of unrelated, difficult-to-express (DTE) proteins. First step is rapid generation of transfected pools with the STEP® vectors. All high expressing surviving pools showed high product quality homogeneity as did monoclonal cell lines obtained from the top pools. Up to 500 µg/mL laronidase was obtained with virtually identical glycosylation profile as reference product. For FVII, cell specific productivity of 0.45 pg/cell/day with 50 IU/µg protein matched highest reported levels of reference product even before process development. Taken together, STEP® vector technology is ideally suited for rapid, small to large-scale production of DTE proteins compared to traditional methods.